Allosteric modulation of conformational dynamics in human Hsp90α: a computational study
- Penkler, David L, Atilgan, Canan, Tastan Bishop, Özlem
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/68531 , vital:29276 , http://dx.doi.org/10.1101/198341
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by co-chaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. Here, we utilize homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially-open conformations. Atomistic simulations of these structures demonstrated that bound ATP stabilizes the dimer by ‘tensing’ each protomer, while ADP and apo configurations ‘relax’ the complex by increasing global flexibility. Dynamic residue network analysis revealed regions of the protein involved in intra-protein communication, and identified several overlapping key communication hubs that correlate with known functional sites. Perturbation response scanning analysis identified several potential residue sites capable of modulating conformational change in favour of interstate conversion. For the ATP-bound open conformation, these sites were found to overlap with known Aha1 and client binding sites, demonstrating how naturally occurring forces associated with co-factor binding could allosterically modulate conformational dynamics.
- Full Text:
- Date Issued: 2017
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/68531 , vital:29276 , http://dx.doi.org/10.1101/198341
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by co-chaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. Here, we utilize homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially-open conformations. Atomistic simulations of these structures demonstrated that bound ATP stabilizes the dimer by ‘tensing’ each protomer, while ADP and apo configurations ‘relax’ the complex by increasing global flexibility. Dynamic residue network analysis revealed regions of the protein involved in intra-protein communication, and identified several overlapping key communication hubs that correlate with known functional sites. Perturbation response scanning analysis identified several potential residue sites capable of modulating conformational change in favour of interstate conversion. For the ATP-bound open conformation, these sites were found to overlap with known Aha1 and client binding sites, demonstrating how naturally occurring forces associated with co-factor binding could allosterically modulate conformational dynamics.
- Full Text:
- Date Issued: 2017
Allosteric Modulation of Human Hsp90α Conformational Dynamics:
- Penkler, David L, Atilgan, Canan, Tastan Bishop, Özlem
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162936 , vital:40998 , https://doi.org/10.1021/acs.jcim.7b00630
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by cochaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. In this study, we utilized homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially open conformations and used these structures as a basis for several molecular dynamics based analyses aimed at elucidating allosteric mechanisms and modulation sites in human Hsp90α.
- Full Text:
- Date Issued: 2018
- Authors: Penkler, David L , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162936 , vital:40998 , https://doi.org/10.1021/acs.jcim.7b00630
- Description: Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by cochaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. In this study, we utilized homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially open conformations and used these structures as a basis for several molecular dynamics based analyses aimed at elucidating allosteric mechanisms and modulation sites in human Hsp90α.
- Full Text:
- Date Issued: 2018
Allosteric pockets and dynamic residue network hubs of falcipain 2 in mutations including those linked to artemisinin resistance
- Okeke, Chiamaka J, Musyoka, Thommas M, Sheik Amamuddy, Olivier, Barozi, Victor, Tastan Bishop, Özlem
- Authors: Okeke, Chiamaka J , Musyoka, Thommas M , Sheik Amamuddy, Olivier , Barozi, Victor , Tastan Bishop, Özlem
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/476585 , vital:77939 , xlink:href="https://doi.org/10.1016/j.csbj.2021.10.011"
- Description: Continually emerging resistant strains of malarial parasites to current drugs present challenges. Understanding the underlying resistance mechanisms, especially those linked to allostery is, thus, highly crucial for drug design. This forms the main concern of the paper through a case study of falcipain 2 (FP-2) and its mutations, some of which are linked to artemisinin (ART) drug resistance. Here, we applied a variety of in silico approaches and tools that we developed recently, together with existing computational tools. This included novel essential dynamics and dynamic residue network (DRN) analysis algorithms. We identified six pockets demonstrating dynamic differences in the presence of some mutations. We observed striking allosteric effects in two mutant proteins. In the presence of M245I, a cryptic pocket was detected via a unique mechanism in which Pocket 2 fused with Pocket 6. In the presence of the A353T mutation, which is located at Pocket 2, the pocket became the most rigid among all protein systems analyzed. Pocket 6 was also highly stable in all cases, except in the presence of M245I mutation. The effect of ART linked mutations was more subtle, and the changes were at residue level. Importantly, we identified an allosteric communication path formed by four unique averaged BC hubs going from the mutated residue to the catalytic site and passing through the interface of three identified pockets. Collectively, we established and demonstrated that we have robust tools and a pipeline that can be applicable to the analysis of mutations.
- Full Text:
- Date Issued: 2021
- Authors: Okeke, Chiamaka J , Musyoka, Thommas M , Sheik Amamuddy, Olivier , Barozi, Victor , Tastan Bishop, Özlem
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/476585 , vital:77939 , xlink:href="https://doi.org/10.1016/j.csbj.2021.10.011"
- Description: Continually emerging resistant strains of malarial parasites to current drugs present challenges. Understanding the underlying resistance mechanisms, especially those linked to allostery is, thus, highly crucial for drug design. This forms the main concern of the paper through a case study of falcipain 2 (FP-2) and its mutations, some of which are linked to artemisinin (ART) drug resistance. Here, we applied a variety of in silico approaches and tools that we developed recently, together with existing computational tools. This included novel essential dynamics and dynamic residue network (DRN) analysis algorithms. We identified six pockets demonstrating dynamic differences in the presence of some mutations. We observed striking allosteric effects in two mutant proteins. In the presence of M245I, a cryptic pocket was detected via a unique mechanism in which Pocket 2 fused with Pocket 6. In the presence of the A353T mutation, which is located at Pocket 2, the pocket became the most rigid among all protein systems analyzed. Pocket 6 was also highly stable in all cases, except in the presence of M245I mutation. The effect of ART linked mutations was more subtle, and the changes were at residue level. Importantly, we identified an allosteric communication path formed by four unique averaged BC hubs going from the mutated residue to the catalytic site and passing through the interface of three identified pockets. Collectively, we established and demonstrated that we have robust tools and a pipeline that can be applicable to the analysis of mutations.
- Full Text:
- Date Issued: 2021
Allosteric site modulators: a case study for falcipains as malarial drug targets
- Musyoka, Thommas M, Tastan Bishop, Özlem
- Authors: Musyoka, Thommas M , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162699 , vital:40974 , https://doi.org/10.21955/gatesopenres.1116459.1
- Description: Fighting against malaria is a never-ending battle. Plasmodium parasites continuously develop resistance to the drugs used against them including the artemisinin-based combination therapies as observed recently in Southeast Asia. The main concern now is whether the resistant parasite strains spread to Africa, where most malaria cases are located. To prevent this, we need to think outside the box. To date, there is no allosteric drug for malaria. Hence, allosteric drug targeting sites and modulators might be a new hope for malarial treatment. In Plasmodium falciparum two cysteine proteases, falcipain-2 (FP-2) and falcipain-3 (FP-3), have been identified as the main hemoglobinases, and are considered as attractive drug targets.
- Full Text:
- Date Issued: 2019
- Authors: Musyoka, Thommas M , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162699 , vital:40974 , https://doi.org/10.21955/gatesopenres.1116459.1
- Description: Fighting against malaria is a never-ending battle. Plasmodium parasites continuously develop resistance to the drugs used against them including the artemisinin-based combination therapies as observed recently in Southeast Asia. The main concern now is whether the resistant parasite strains spread to Africa, where most malaria cases are located. To prevent this, we need to think outside the box. To date, there is no allosteric drug for malaria. Hence, allosteric drug targeting sites and modulators might be a new hope for malarial treatment. In Plasmodium falciparum two cysteine proteases, falcipain-2 (FP-2) and falcipain-3 (FP-3), have been identified as the main hemoglobinases, and are considered as attractive drug targets.
- Full Text:
- Date Issued: 2019
AMBER force field parameters for the Zn (II) ions of the tunneling-fold enzymes GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase
- Khairallah, Afrah, Tastan Bishop, Özlem, Moses, Vuyani
- Authors: Khairallah, Afrah , Tastan Bishop, Özlem , Moses, Vuyani
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429360 , vital:72604 , xlink:href="https://doi.org/10.1080/07391102.2020.1796800"
- Description: The folate biosynthesis pathway is an essential pathway for cell growth and survival. Folate derivatives serve as a source of the one-carbon units in several intracellular metabolic reactions. Rapidly dividing cells rely heavily on the availability of folate derivatives for their proliferation. As a result, drugs targeting this pathway have shown to be effective against tumor cells and pathogens, but drug resistance against the available antifolate drugs emerged quickly. Therefore, there is a need to develop new treatment strategies and identify alternative metabolic targets. The two de novo folate biosynthesis pathway enzymes, GTP cyclohydrolase I (GCH1) and 6-pyruvoyl tetrahydropterin synthase (PTPS), can provide an alternative strategy to overcome the drug resistance that emerged in the two primary targeted enzymes dihydrofolate reductase and dihydropteroate synthase. Both GCH1 and PTPS enzymes contain Zn2+ ions in their active sites, and to accurately study their dynamic behaviors using all-atom molecular dynamics (MD) simulations, appropriate parameters that can describe their metal sites should be developed and validated. In this study, force field parameters of the GCH1 and PTPS metal centers were generated using quantum mechanics (QM) calculations and then validated through MD simulations to ensure their accuracy in describing and maintaining the Zn2+ ion coordination environment. The derived force field parameters will provide accurate and reliable MD simulations involving these two enzymes for future in-silico identification of drug candidates against the GCH1 and PTPS enzymes.
- Full Text:
- Date Issued: 2020
- Authors: Khairallah, Afrah , Tastan Bishop, Özlem , Moses, Vuyani
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429360 , vital:72604 , xlink:href="https://doi.org/10.1080/07391102.2020.1796800"
- Description: The folate biosynthesis pathway is an essential pathway for cell growth and survival. Folate derivatives serve as a source of the one-carbon units in several intracellular metabolic reactions. Rapidly dividing cells rely heavily on the availability of folate derivatives for their proliferation. As a result, drugs targeting this pathway have shown to be effective against tumor cells and pathogens, but drug resistance against the available antifolate drugs emerged quickly. Therefore, there is a need to develop new treatment strategies and identify alternative metabolic targets. The two de novo folate biosynthesis pathway enzymes, GTP cyclohydrolase I (GCH1) and 6-pyruvoyl tetrahydropterin synthase (PTPS), can provide an alternative strategy to overcome the drug resistance that emerged in the two primary targeted enzymes dihydrofolate reductase and dihydropteroate synthase. Both GCH1 and PTPS enzymes contain Zn2+ ions in their active sites, and to accurately study their dynamic behaviors using all-atom molecular dynamics (MD) simulations, appropriate parameters that can describe their metal sites should be developed and validated. In this study, force field parameters of the GCH1 and PTPS metal centers were generated using quantum mechanics (QM) calculations and then validated through MD simulations to ensure their accuracy in describing and maintaining the Zn2+ ion coordination environment. The derived force field parameters will provide accurate and reliable MD simulations involving these two enzymes for future in-silico identification of drug candidates against the GCH1 and PTPS enzymes.
- Full Text:
- Date Issued: 2020
AMBER force field parameters for the Zn (II) ions of the tunneling-fold enzymes GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase:
- Khairallah, Afrah, Tastan Bishop, Özlem, Moses, Vuyani
- Authors: Khairallah, Afrah , Tastan Bishop, Özlem , Moses, Vuyani
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163068 , vital:41009 , DOI: 10.1080/07391102.2020.1796800
- Description: The folate biosynthesis pathway is an essential pathway for cell growth and survival. Folate derivatives serve as a source of the one-carbon units in several intracellular metabolic reactions. Rapidly dividing cells rely heavily on the availability of folate derivatives for their proliferation. As a result, drugs targeting this pathway have shown to be effective against tumor cells and pathogens, but drug resistance against the available antifolate drugs emerged quickly. Therefore, there is a need to develop new treatment strategies and identify alternative metabolic targets. The two de novo folate biosynthesis pathway enzymes, GTP cyclohydrolase I (GCH1) and 6-pyruvoyl tetrahydropterin synthase (PTPS), can provide an alternative strategy to overcome the drug resistance that emerged in the two primary targeted enzymes dihydrofolate reductase and dihydropteroate synthase.
- Full Text:
- Date Issued: 2020
- Authors: Khairallah, Afrah , Tastan Bishop, Özlem , Moses, Vuyani
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163068 , vital:41009 , DOI: 10.1080/07391102.2020.1796800
- Description: The folate biosynthesis pathway is an essential pathway for cell growth and survival. Folate derivatives serve as a source of the one-carbon units in several intracellular metabolic reactions. Rapidly dividing cells rely heavily on the availability of folate derivatives for their proliferation. As a result, drugs targeting this pathway have shown to be effective against tumor cells and pathogens, but drug resistance against the available antifolate drugs emerged quickly. Therefore, there is a need to develop new treatment strategies and identify alternative metabolic targets. The two de novo folate biosynthesis pathway enzymes, GTP cyclohydrolase I (GCH1) and 6-pyruvoyl tetrahydropterin synthase (PTPS), can provide an alternative strategy to overcome the drug resistance that emerged in the two primary targeted enzymes dihydrofolate reductase and dihydropteroate synthase.
- Full Text:
- Date Issued: 2020
Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study
- Nyamai, Dorothy Wavinya, Tastan Bishop, Özlem
- Authors: Nyamai, Dorothy Wavinya , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148368 , vital:38733 , DOI: 10.1101/440891
- Description: Treatment of parasitic diseases has been challenging due to evolution of drug resistant parasites, and thus there is need to identify new class of drugs and drug targets. Protein translation is important for survival of malarial parasite, Plasmodium, and the pathway is present in all of its life cycle stages. Aminoacyl tRNA synthetases are primary enzymes in protein translation as they catalyse amino acid addition to the cognate tRNA. This study sought to understand differences between Plasmodium and human aminoacyl tRNA synthetases through bioinformatics analysis.
- Full Text:
- Date Issued: 2018
- Authors: Nyamai, Dorothy Wavinya , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148368 , vital:38733 , DOI: 10.1101/440891
- Description: Treatment of parasitic diseases has been challenging due to evolution of drug resistant parasites, and thus there is need to identify new class of drugs and drug targets. Protein translation is important for survival of malarial parasite, Plasmodium, and the pathway is present in all of its life cycle stages. Aminoacyl tRNA synthetases are primary enzymes in protein translation as they catalyse amino acid addition to the cognate tRNA. This study sought to understand differences between Plasmodium and human aminoacyl tRNA synthetases through bioinformatics analysis.
- Full Text:
- Date Issued: 2018
Analysis of non-peptidic compounds as potential malarial inhibitors against plasmodial cysteine proteases via integrated virtual screening workflow
- Musyoka, Thommas M, Kanzi, Aquillah M, Lobb, Kevin A, Tastan Bishop, Özlem
- Authors: Musyoka, Thommas M , Kanzi, Aquillah M , Lobb, Kevin A , Tastan Bishop, Özlem
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123074 , vital:35403 , https://doi.10.1080/07391102.2015.1108231
- Description: Malaria is an infectious disease caused by a diverse group of erythrocytic protozoan parasites of the genus Plasmodium. It remains an exigent public health problem in the tropical areas of Africa, South America and parts of Asia and continues to take its toll in morbidity and mortality with half of the world’s population under a permanent risk of infection leading to more than half a million deaths annually (WHO, 2013). Five Plasmodium species, namely P. falciparum (Pf ), P. vivax (Pv), P. ovale (Po), P. malariae (Pm) and P. knowlesi (Pk), are known to infect humans with Pf responsible for more than 90% of the malarial fatalities reported in sub-Saharan Africa. The predominance of Pf is attributed to its adaptability (Ashley, McGready, Proux, & Nosten, 2006; Prugnolle et al., 2011). Although the high occurrence of the Duffy negative trait among African populations lowers the threat posed by Pv, it is the most frequent and widely causative agent of benign tertian malaria in other parts of the world (Mendis, Sina, Marchesini, & Carter, 2001). In addition to the listed human malarial parasite forms, several other Plasmodium species, which infect non-human laboratory models, have been identified and are of significant importance in understanding the parasite biology, the host–parasite interactions and in the drug development process (Langhorne et al., 2011).
- Full Text:
- Date Issued: 2016
- Authors: Musyoka, Thommas M , Kanzi, Aquillah M , Lobb, Kevin A , Tastan Bishop, Özlem
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123074 , vital:35403 , https://doi.10.1080/07391102.2015.1108231
- Description: Malaria is an infectious disease caused by a diverse group of erythrocytic protozoan parasites of the genus Plasmodium. It remains an exigent public health problem in the tropical areas of Africa, South America and parts of Asia and continues to take its toll in morbidity and mortality with half of the world’s population under a permanent risk of infection leading to more than half a million deaths annually (WHO, 2013). Five Plasmodium species, namely P. falciparum (Pf ), P. vivax (Pv), P. ovale (Po), P. malariae (Pm) and P. knowlesi (Pk), are known to infect humans with Pf responsible for more than 90% of the malarial fatalities reported in sub-Saharan Africa. The predominance of Pf is attributed to its adaptability (Ashley, McGready, Proux, & Nosten, 2006; Prugnolle et al., 2011). Although the high occurrence of the Duffy negative trait among African populations lowers the threat posed by Pv, it is the most frequent and widely causative agent of benign tertian malaria in other parts of the world (Mendis, Sina, Marchesini, & Carter, 2001). In addition to the listed human malarial parasite forms, several other Plasmodium species, which infect non-human laboratory models, have been identified and are of significant importance in understanding the parasite biology, the host–parasite interactions and in the drug development process (Langhorne et al., 2011).
- Full Text:
- Date Issued: 2016
Analysis of protein thermostability enhancing factors in industrially important thermus bacteria species
- Kumwenda, Benjamin, Litthauer, Derek, Tastan Bishop, Özlem, Reva, Oleg
- Authors: Kumwenda, Benjamin , Litthauer, Derek , Tastan Bishop, Özlem , Reva, Oleg
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123085 , vital:35404 , https://doi.10.4137/EBO.S12539
- Description: Elucidation of evolutionary factors that enhance protein thermostability is a critical problem and was the focus of this work on Thermus species. Pairs of orthologous sequences of T. scotoductus SA-01 and T. thermophilus HB27, with the largest negative minimum folding energy (MFE) as predicted by the UNAFold algorithm, were statistically analyzed. Favored substitutions of amino acids residues and their properties were determined. Substitutions were analyzed in modeled protein structures to determine their locations and contribution to energy differences using PyMOL and FoldX programs respectively. Dominant trends in amino acid substitutions consistent with differences in thermostability between orthologous sequences were observed. T. thermophilus thermophilic proteins showed an increase in non-polar, tiny, and charged amino acids. An abundance of alanine substituted by serine and threonine, as well as arginine substituted by glutamine and lysine was observed in T. thermophilus HB27. Structural comparison showed that stabilizing mutations occurred on surfaces and loops in protein structures.
- Full Text:
- Date Issued: 2013
- Authors: Kumwenda, Benjamin , Litthauer, Derek , Tastan Bishop, Özlem , Reva, Oleg
- Date: 2013
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123085 , vital:35404 , https://doi.10.4137/EBO.S12539
- Description: Elucidation of evolutionary factors that enhance protein thermostability is a critical problem and was the focus of this work on Thermus species. Pairs of orthologous sequences of T. scotoductus SA-01 and T. thermophilus HB27, with the largest negative minimum folding energy (MFE) as predicted by the UNAFold algorithm, were statistically analyzed. Favored substitutions of amino acids residues and their properties were determined. Substitutions were analyzed in modeled protein structures to determine their locations and contribution to energy differences using PyMOL and FoldX programs respectively. Dominant trends in amino acid substitutions consistent with differences in thermostability between orthologous sequences were observed. T. thermophilus thermophilic proteins showed an increase in non-polar, tiny, and charged amino acids. An abundance of alanine substituted by serine and threonine, as well as arginine substituted by glutamine and lysine was observed in T. thermophilus HB27. Structural comparison showed that stabilizing mutations occurred on surfaces and loops in protein structures.
- Full Text:
- Date Issued: 2013
Anti-HIV-1 integrase potency of methylgallate from Alchornea cordifolia using in vitro and in silico approaches:
- Noundou, Xavier S, Musyoka, Thommas M, Moses, Vuyani, Ndinteh, Derek T, Mnkandhla, Dumisani, Hoppe, Heinrich C, Tastan Bishop, Özlem, Krause, Rui W M
- Authors: Noundou, Xavier S , Musyoka, Thommas M , Moses, Vuyani , Ndinteh, Derek T , Mnkandhla, Dumisani , Hoppe, Heinrich C , Tastan Bishop, Özlem , Krause, Rui W M
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162975 , vital:41001 , https://0-doi.org.wam.seals.ac.za/10.1038/s41598-019-41403-x
- Description: According to the 2018 report of the United Nations Programme on HIV/AIDS (UNAIDS), acquired immune deficiency syndrome (AIDS), a disease caused by the human immunodeficiency virus (HIV), remains a significant public health problem. The non-existence of a cure or effective vaccine for the disease and the associated emergence of resistant viral strains imply an urgent need for the discovery of novel anti-HIV drug candidates. The current study aimed to identify potential anti-retroviral compounds from Alchornea cordifolia.
- Full Text:
- Date Issued: 2019
- Authors: Noundou, Xavier S , Musyoka, Thommas M , Moses, Vuyani , Ndinteh, Derek T , Mnkandhla, Dumisani , Hoppe, Heinrich C , Tastan Bishop, Özlem , Krause, Rui W M
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162975 , vital:41001 , https://0-doi.org.wam.seals.ac.za/10.1038/s41598-019-41403-x
- Description: According to the 2018 report of the United Nations Programme on HIV/AIDS (UNAIDS), acquired immune deficiency syndrome (AIDS), a disease caused by the human immunodeficiency virus (HIV), remains a significant public health problem. The non-existence of a cure or effective vaccine for the disease and the associated emergence of resistant viral strains imply an urgent need for the discovery of novel anti-HIV drug candidates. The current study aimed to identify potential anti-retroviral compounds from Alchornea cordifolia.
- Full Text:
- Date Issued: 2019
Antiviral Mechanisms of N-Phenyl Benzamides on Coxsackie Virus A9
- Laajala, Mira, Kalander, Kerttu, Consalvi, Sara, Sheik Amamuddy, Olivier, Tastan Bishop, Özlem, Biava, Mariangela, Poce, Giovanna, Marjomäki, Varpu
- Authors: Laajala, Mira , Kalander, Kerttu , Consalvi, Sara , Sheik Amamuddy, Olivier , Tastan Bishop, Özlem , Biava, Mariangela , Poce, Giovanna , Marjomäki, Varpu
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/474448 , vital:77708 , https://doi.org/10.3390/pharmaceutics15031028
- Description: Enteroviruses are one of the most abundant groups of viruses infecting humans, and yet there are no approved antivirals against them. To find effective antiviral compounds against enterovirus B group viruses, an in-house chemical library was screened. The most effective compounds against Coxsackieviruses B3 (CVB3) and A9 (CVA9) were CL212 and CL213, two N-phenyl benzamides. Both compounds were more effective against CVA9 and CL213 gave a better EC50 value of 1 µM with high a specificity index of 140. Both drugs were most effective when incubated directly with viruses suggesting that they mainly bound to the virions. A real-time uncoating assay showed that the compounds stabilized the virions and radioactive sucrose gradient as well as TEM confirmed that the viruses stayed intact. A docking assay, taking into account larger areas around the 2-and 3-fold axes of CVA9 and CVB3, suggested that the hydrophobic pocket gives the strongest binding to CVA9 but revealed another binding site around the 3-fold axis which could contribute to the binding of the compounds. Together, our data support a direct antiviral mechanism against the virus capsid and suggest that the compounds bind to the hydrophobic pocket and 3-fold axis area resulting in the stabilization of the virion
- Full Text:
- Date Issued: 2023
- Authors: Laajala, Mira , Kalander, Kerttu , Consalvi, Sara , Sheik Amamuddy, Olivier , Tastan Bishop, Özlem , Biava, Mariangela , Poce, Giovanna , Marjomäki, Varpu
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/474448 , vital:77708 , https://doi.org/10.3390/pharmaceutics15031028
- Description: Enteroviruses are one of the most abundant groups of viruses infecting humans, and yet there are no approved antivirals against them. To find effective antiviral compounds against enterovirus B group viruses, an in-house chemical library was screened. The most effective compounds against Coxsackieviruses B3 (CVB3) and A9 (CVA9) were CL212 and CL213, two N-phenyl benzamides. Both compounds were more effective against CVA9 and CL213 gave a better EC50 value of 1 µM with high a specificity index of 140. Both drugs were most effective when incubated directly with viruses suggesting that they mainly bound to the virions. A real-time uncoating assay showed that the compounds stabilized the virions and radioactive sucrose gradient as well as TEM confirmed that the viruses stayed intact. A docking assay, taking into account larger areas around the 2-and 3-fold axes of CVA9 and CVB3, suggested that the hydrophobic pocket gives the strongest binding to CVA9 but revealed another binding site around the 3-fold axis which could contribute to the binding of the compounds. Together, our data support a direct antiviral mechanism against the virus capsid and suggest that the compounds bind to the hydrophobic pocket and 3-fold axis area resulting in the stabilization of the virion
- Full Text:
- Date Issued: 2023
Bioinformatic characterization of type-specific sequence and structural features in auxiliary activity family 9 proteins:
- Moses, Vuyani, Hatherley, Rowan, Tastan Bishop, Özlem
- Authors: Moses, Vuyani , Hatherley, Rowan , Tastan Bishop, Özlem
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148358 , vital:38732 , DOI: 10.1186/s13068-016-0655-2
- Description: Due to the impending depletion of fossil fuels, it has become important to identify alternative energy sources. The biofuel industry has proven to be a promising alternative. However, owing to the complex nature of plant biomass, hence the degradation, biofuel production remains a challenge. The copper-dependent Auxiliary Activity family 9 (AA9) proteins have been found to act synergistically with other cellulose-degrading enzymes resulting in an increased rate of cellulose breakdown. AA9 proteins are lytic polysaccharide monooxygenase (LPMO) enzymes, otherwise known as polysaccharide monooxygenases (PMOs). They are further classified as Type 1, 2 or 3 PMOs, depending on the different cleavage products formed. As AA9 proteins are known to exhibit low sequence conservation, the analysis of unique features of AA9 domains of these enzymes should provide insights for the better understanding of how different AA9 PMO types function.
- Full Text:
- Date Issued: 2016
- Authors: Moses, Vuyani , Hatherley, Rowan , Tastan Bishop, Özlem
- Date: 2016
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148358 , vital:38732 , DOI: 10.1186/s13068-016-0655-2
- Description: Due to the impending depletion of fossil fuels, it has become important to identify alternative energy sources. The biofuel industry has proven to be a promising alternative. However, owing to the complex nature of plant biomass, hence the degradation, biofuel production remains a challenge. The copper-dependent Auxiliary Activity family 9 (AA9) proteins have been found to act synergistically with other cellulose-degrading enzymes resulting in an increased rate of cellulose breakdown. AA9 proteins are lytic polysaccharide monooxygenase (LPMO) enzymes, otherwise known as polysaccharide monooxygenases (PMOs). They are further classified as Type 1, 2 or 3 PMOs, depending on the different cleavage products formed. As AA9 proteins are known to exhibit low sequence conservation, the analysis of unique features of AA9 domains of these enzymes should provide insights for the better understanding of how different AA9 PMO types function.
- Full Text:
- Date Issued: 2016
Bioinformatics and data analysis in microbiology:
- Authors: Tastan Bishop, Özlem
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/148104 , vital:38710 , ISBN 9781908230737 , https://books.google.co.za/books?id=-G07DwAAQBAJanddq=Bioinformatics+and+data+analysis+in+microbiologyandsource=gbs_navlinks_s
- Description: The rapid advancement of sequencing techniques, coupled with the new methodologies of bioinformatics to handle large-scale data analysis, are providing exciting opportunities for us to understand microbial communities from a variety of environments beyond previous imagination. This book provides invaluable, up-to-date and detailed information on various aspects of bioinformatics data analysis with applications to microbiology. It describes a number of different useful bioinformatics tools, makes links to some wet-lab techniques, explains different approaches to tackle a problem, talks about current challenges and limitations, gives examples of applications of bioinformatics methods to microbiology, and discusses future trends. The chapters include topics such as genome sequencing techniques, assembly, SNP analysis, annotation, comparative genomics, microbial community profiling, metagenomics, phylogenetic microarrays, barcoding and more. Each chapter is written by scientists who are expert in the field, and is peer-reviewed. Bioinformatics and Data Analysis in Microbiology is an essential book for researchers, lecturers and students involved in microbiology, bioinformatics and genome analysis.
- Full Text:
- Date Issued: 2014
- Authors: Tastan Bishop, Özlem
- Date: 2014
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/148104 , vital:38710 , ISBN 9781908230737 , https://books.google.co.za/books?id=-G07DwAAQBAJanddq=Bioinformatics+and+data+analysis+in+microbiologyandsource=gbs_navlinks_s
- Description: The rapid advancement of sequencing techniques, coupled with the new methodologies of bioinformatics to handle large-scale data analysis, are providing exciting opportunities for us to understand microbial communities from a variety of environments beyond previous imagination. This book provides invaluable, up-to-date and detailed information on various aspects of bioinformatics data analysis with applications to microbiology. It describes a number of different useful bioinformatics tools, makes links to some wet-lab techniques, explains different approaches to tackle a problem, talks about current challenges and limitations, gives examples of applications of bioinformatics methods to microbiology, and discusses future trends. The chapters include topics such as genome sequencing techniques, assembly, SNP analysis, annotation, comparative genomics, microbial community profiling, metagenomics, phylogenetic microarrays, barcoding and more. Each chapter is written by scientists who are expert in the field, and is peer-reviewed. Bioinformatics and Data Analysis in Microbiology is an essential book for researchers, lecturers and students involved in microbiology, bioinformatics and genome analysis.
- Full Text:
- Date Issued: 2014
Bioinformatics education—perspectives and challenges out of Africa
- Tastan Bishop, Özlem, Adebiyi, Ezekiel F, Alzohairy, Ahmed M, Everett, Dean B, Ghedira, Kais, Ghouila, Amel, Kumuthini, Judit, Mulder, Nicola J, Panji, Sumir, Patterton, Hugh-G
- Authors: Tastan Bishop, Özlem , Adebiyi, Ezekiel F , Alzohairy, Ahmed M , Everett, Dean B , Ghedira, Kais , Ghouila, Amel , Kumuthini, Judit , Mulder, Nicola J , Panji, Sumir , Patterton, Hugh-G
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123244 , vital:35420 , https://doi.10.1093/bib/bbu022
- Description: The discipline of bioinformatics has developed rapidly since the complete sequencing of the first genomes in the 1990s.The development of many high-throughput techniques during the last decades has ensured that bioinformatics has grown into a discipline that overlaps with, and is required for, the modern practice of virtually every field in the life sciences. This has placed a scientific premium on the availability of skilled bioinformaticians, a qualification that is extremely scarce on the African continent. The reasons for this are numerous, although the absence of a skilled bioinformatician at academic institutions to initiate a training process and build sustained capacity seems to be a common African shortcoming.This dearth of bioinformatics expertise has had a knock-on effect on the establishment of many modern high-throughput projects at African institutes, including the comprehensive and systematic analysis of genomes from African populations, which are among the most genetically diverse anywhere on the planet. Recent funding initiatives from the National Institutes of Health and theWellcomeTrust are aimed at ameliorating this shortcoming. In this paper, we discuss the problems that have limited the establishment of the bioinformatics field in Africa, as well as propose specific actions that will help with the education and training of bioinformaticians on the continent. This is an absolute requirement in anticipation of a boom in high-throughput approaches to human health issues unique to data from African populations.
- Full Text:
- Date Issued: 2014
- Authors: Tastan Bishop, Özlem , Adebiyi, Ezekiel F , Alzohairy, Ahmed M , Everett, Dean B , Ghedira, Kais , Ghouila, Amel , Kumuthini, Judit , Mulder, Nicola J , Panji, Sumir , Patterton, Hugh-G
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123244 , vital:35420 , https://doi.10.1093/bib/bbu022
- Description: The discipline of bioinformatics has developed rapidly since the complete sequencing of the first genomes in the 1990s.The development of many high-throughput techniques during the last decades has ensured that bioinformatics has grown into a discipline that overlaps with, and is required for, the modern practice of virtually every field in the life sciences. This has placed a scientific premium on the availability of skilled bioinformaticians, a qualification that is extremely scarce on the African continent. The reasons for this are numerous, although the absence of a skilled bioinformatician at academic institutions to initiate a training process and build sustained capacity seems to be a common African shortcoming.This dearth of bioinformatics expertise has had a knock-on effect on the establishment of many modern high-throughput projects at African institutes, including the comprehensive and systematic analysis of genomes from African populations, which are among the most genetically diverse anywhere on the planet. Recent funding initiatives from the National Institutes of Health and theWellcomeTrust are aimed at ameliorating this shortcoming. In this paper, we discuss the problems that have limited the establishment of the bioinformatics field in Africa, as well as propose specific actions that will help with the education and training of bioinformaticians on the continent. This is an absolute requirement in anticipation of a boom in high-throughput approaches to human health issues unique to data from African populations.
- Full Text:
- Date Issued: 2014
Characterisation of plasmodial transketolases and identification of potential inhibitors: an in silico study
- Boateng, Rita A, Tastan Bishop, Özlem, Musyoka, Thommas M
- Authors: Boateng, Rita A , Tastan Bishop, Özlem , Musyoka, Thommas M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429372 , vital:72605 , xlink:href="https://doi.org/10.1186/s12936-020-03512-1"
- Description: Plasmodial transketolase (PTKT) enzyme is one of the novel pharmacological targets being explored as potential anti-malarial drug target due to its functional role and low sequence identity to the human enzyme. Despite this, features contributing to such have not been exploited for anti-malarial drug design. Additionally, there are no anti-malarial drugs targeting PTKTs whereas the broad activity of these inhibitors against PTKTs from other Plasmodium spp. is yet to be reported. This study characterises different PTKTs [Plasmodium falciparum (PfTKT), Plasmodium vivax (PvTKT), Plasmodium ovale (PoTKT), Plasmodium malariae (PmTKT) and Plasmodium knowlesi (PkTKT) and the human homolog (HsTKT)] to identify key sequence and structural based differences as well as the identification of selective potential inhibitors against PTKTs.
- Full Text:
- Date Issued: 2020
- Authors: Boateng, Rita A , Tastan Bishop, Özlem , Musyoka, Thommas M
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429372 , vital:72605 , xlink:href="https://doi.org/10.1186/s12936-020-03512-1"
- Description: Plasmodial transketolase (PTKT) enzyme is one of the novel pharmacological targets being explored as potential anti-malarial drug target due to its functional role and low sequence identity to the human enzyme. Despite this, features contributing to such have not been exploited for anti-malarial drug design. Additionally, there are no anti-malarial drugs targeting PTKTs whereas the broad activity of these inhibitors against PTKTs from other Plasmodium spp. is yet to be reported. This study characterises different PTKTs [Plasmodium falciparum (PfTKT), Plasmodium vivax (PvTKT), Plasmodium ovale (PoTKT), Plasmodium malariae (PmTKT) and Plasmodium knowlesi (PkTKT) and the human homolog (HsTKT)] to identify key sequence and structural based differences as well as the identification of selective potential inhibitors against PTKTs.
- Full Text:
- Date Issued: 2020
Characterizing early drug resistance-related events using geometric ensembles from HIV protease dynamics:
- Sheik Amamuddy, Olivier, Bishop, Nigel T, Tastan Bishop, Özlem
- Authors: Sheik Amamuddy, Olivier , Bishop, Nigel T , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148126 , vital:38712 , DOI: 10.1038/s41598-018-36041-8
- Description: The use of antiretrovirals (ARVs) has drastically improved the life quality and expectancy of HIV patients since their introduction in health care. Several millions are still afflicted worldwide by HIV and ARV resistance is a constant concern for both healthcare practitioners and patients, as while treatment options are finite, the virus constantly adapts via complex mutation patterns to select for resistant strains under the pressure of drug treatment. The HIV protease is a crucial enzyme for viral maturation and has been a game changing drug target since the first application. Due to similarities in protease inhibitor designs, drug cross-resistance is not uncommon across ARVs of the same class.
- Full Text:
- Date Issued: 2018
- Authors: Sheik Amamuddy, Olivier , Bishop, Nigel T , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148126 , vital:38712 , DOI: 10.1038/s41598-018-36041-8
- Description: The use of antiretrovirals (ARVs) has drastically improved the life quality and expectancy of HIV patients since their introduction in health care. Several millions are still afflicted worldwide by HIV and ARV resistance is a constant concern for both healthcare practitioners and patients, as while treatment options are finite, the virus constantly adapts via complex mutation patterns to select for resistant strains under the pressure of drug treatment. The HIV protease is a crucial enzyme for viral maturation and has been a game changing drug target since the first application. Due to similarities in protease inhibitor designs, drug cross-resistance is not uncommon across ARVs of the same class.
- Full Text:
- Date Issued: 2018
Comparative structural bioinformatics analysis of Bacillus amyloliquefaciens chemotaxis proteins within Bacillus subtilis group
- Yssel, Anna, Reva, Oleg, Tastan Bishop, Özlem
- Authors: Yssel, Anna , Reva, Oleg , Tastan Bishop, Özlem
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123966 , vital:35521 , https://doi.10.1007/s00253-011-3582-y
- Description: Chemotaxis is a process in which bacteria sense their chemical environment and move towards more favorable conditions. Since plant colonization by bacteria is a multifaceted process which requires a response to the complex chemical environment, a finely tuned and sensitive chemotaxis system is needed. Members of the Bacillus subtilis group including Bacillus amyloliquefaciens are industrially important, for example, as bio-pesticides. The group exhibits plant growth-promoting characteristics, with different specificity towards certain host plants. Therefore, we hypothesize that while the principal molecular mechanisms of bacterial chemotaxis may be conserved, the bacterial chemotaxis system may need an evolutionary tweaking to adapt it to specific requirements, particularly in the process of evolution of free-living soil organisms, towards plant colonization behaviour. To date, almost nothing is known about what parts of the chemotaxis proteins are subjected to positive amino acid substitutions, involved in adjusting the chemotaxis system of bacteria during speciation. In this novel study, positively selected and purified sites of chemotaxis proteins were calculated, and these residues were mapped onto homology models that were built for the chemotaxis proteins, in an attempt to understand the spatial evolution of the chemotaxis proteins. Various positively selected amino acids were identified in semi-conserved regions of the proteins away from the known active sites.
- Full Text:
- Date Issued: 2011
- Authors: Yssel, Anna , Reva, Oleg , Tastan Bishop, Özlem
- Date: 2011
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/123966 , vital:35521 , https://doi.10.1007/s00253-011-3582-y
- Description: Chemotaxis is a process in which bacteria sense their chemical environment and move towards more favorable conditions. Since plant colonization by bacteria is a multifaceted process which requires a response to the complex chemical environment, a finely tuned and sensitive chemotaxis system is needed. Members of the Bacillus subtilis group including Bacillus amyloliquefaciens are industrially important, for example, as bio-pesticides. The group exhibits plant growth-promoting characteristics, with different specificity towards certain host plants. Therefore, we hypothesize that while the principal molecular mechanisms of bacterial chemotaxis may be conserved, the bacterial chemotaxis system may need an evolutionary tweaking to adapt it to specific requirements, particularly in the process of evolution of free-living soil organisms, towards plant colonization behaviour. To date, almost nothing is known about what parts of the chemotaxis proteins are subjected to positive amino acid substitutions, involved in adjusting the chemotaxis system of bacteria during speciation. In this novel study, positively selected and purified sites of chemotaxis proteins were calculated, and these residues were mapped onto homology models that were built for the chemotaxis proteins, in an attempt to understand the spatial evolution of the chemotaxis proteins. Various positively selected amino acids were identified in semi-conserved regions of the proteins away from the known active sites.
- Full Text:
- Date Issued: 2011
Comparing sequence and structure of falcipains and human homologs at prodomain and catalytic active site for malarial peptide based inhibitor design:
- Musyoka, Thommas M, Njuguna, Joyce N, Tastan Bishop, Özlem
- Authors: Musyoka, Thommas M , Njuguna, Joyce N , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162962 , vital:41000 , https://0-doi.org.wam.seals.ac.za/10.1186/s12936-019-2790-2
- Description: Falcipains are major cysteine proteases of Plasmodium falciparum involved in haemoglobin degradation and remain attractive anti-malarial drug targets. Several inhibitors against these proteases have been identified, yet none of them has been approved for malaria treatment. Other Plasmodium species also possess highly homologous proteins to falcipains. For selective therapeutic targeting, identification of sequence and structure differences with homologous human cathepsins is necessary. The substrate processing activity of these proteins is tightly controlled via a prodomain segment occluding the active site which is chopped under low pH conditions exposing the catalytic site. Current work characterizes these proteases to identify residues mediating the prodomain regulatory function for the design of peptide based anti-malarial inhibitors.
- Full Text:
- Date Issued: 2019
- Authors: Musyoka, Thommas M , Njuguna, Joyce N , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162962 , vital:41000 , https://0-doi.org.wam.seals.ac.za/10.1186/s12936-019-2790-2
- Description: Falcipains are major cysteine proteases of Plasmodium falciparum involved in haemoglobin degradation and remain attractive anti-malarial drug targets. Several inhibitors against these proteases have been identified, yet none of them has been approved for malaria treatment. Other Plasmodium species also possess highly homologous proteins to falcipains. For selective therapeutic targeting, identification of sequence and structure differences with homologous human cathepsins is necessary. The substrate processing activity of these proteins is tightly controlled via a prodomain segment occluding the active site which is chopped under low pH conditions exposing the catalytic site. Current work characterizes these proteases to identify residues mediating the prodomain regulatory function for the design of peptide based anti-malarial inhibitors.
- Full Text:
- Date Issued: 2019
Comparing sequence and structure of falcipains and human homologs at prodomain and catalytic active site for malarial peptide-based inhibitor design:
- Musyoka, Thommas M, Njuguna, Joyce N, Tastan Bishop, Özlem
- Authors: Musyoka, Thommas M , Njuguna, Joyce N , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148392 , vital:38735 , DOI: 10.1101/381566
- Description: Falcipains are major cysteine proteases of Plasmodium falciparum involved in haemoglobin degradation and remain attractive anti-malarial drug targets. Several inhibitors against these proteases have been identified, yet none of them has been approved for malaria treatment. Other Plasmodium species also possess highly homologous proteins to falcipains. For selective therapeutic targeting, identification of sequence and structure differences with homologous human cathepsins is necessary. The substrate processing activity of these proteins is tightly controlled via a prodomain segment occluding the active site which is chopped under low pH conditions exposing the catalytic site. Current work characterizes these proteases to identify residues mediating the prodomain regulatory function for the design of peptide based anti-malarial inhibitors.
- Full Text:
- Date Issued: 2018
- Authors: Musyoka, Thommas M , Njuguna, Joyce N , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148392 , vital:38735 , DOI: 10.1101/381566
- Description: Falcipains are major cysteine proteases of Plasmodium falciparum involved in haemoglobin degradation and remain attractive anti-malarial drug targets. Several inhibitors against these proteases have been identified, yet none of them has been approved for malaria treatment. Other Plasmodium species also possess highly homologous proteins to falcipains. For selective therapeutic targeting, identification of sequence and structure differences with homologous human cathepsins is necessary. The substrate processing activity of these proteins is tightly controlled via a prodomain segment occluding the active site which is chopped under low pH conditions exposing the catalytic site. Current work characterizes these proteases to identify residues mediating the prodomain regulatory function for the design of peptide based anti-malarial inhibitors.
- Full Text:
- Date Issued: 2018
Computational analysis of missense mutations from the human Macrophage Migration Inhibitory Factor (MIF) protein by Molecular Dynamics Simulations and Dynamic Residue Network Analysis:
- Kimuda, Phillip M, Brown, David K, Sheik Amamuddy, Olivier, Ross, Caroline J, Matovu, Enock, Tastan Bishop, Özlem
- Authors: Kimuda, Phillip M , Brown, David K , Sheik Amamuddy, Olivier , Ross, Caroline J , Matovu, Enock , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163238 , vital:41021 , https://doi.org/10.21955/aasopenres.1115054.1
- Description: Missense mutations are changes in the DNA that result in a change in the amino acid sequence. Depending on their location within the protein they can have a negative impact on how the protein functions. This is especially important for proteins involved in the body’s response to infection and diseases. Macrophage migration inhibitory factor (MIF) is one such protein that functions to recruit white blood cells to sites of inflammation.
- Full Text:
- Date Issued: 2019
- Authors: Kimuda, Phillip M , Brown, David K , Sheik Amamuddy, Olivier , Ross, Caroline J , Matovu, Enock , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163238 , vital:41021 , https://doi.org/10.21955/aasopenres.1115054.1
- Description: Missense mutations are changes in the DNA that result in a change in the amino acid sequence. Depending on their location within the protein they can have a negative impact on how the protein functions. This is especially important for proteins involved in the body’s response to infection and diseases. Macrophage migration inhibitory factor (MIF) is one such protein that functions to recruit white blood cells to sites of inflammation.
- Full Text:
- Date Issued: 2019