Plasmodium falciparum Hop: detailed analysis on complex formation with Hsp70 and Hsp90
- Hatherley, Rowan, Clitheroe, Crystal-Leigh, Faya, Ngonidzashe, Tastan Bishop, Özlem
- Authors: Hatherley, Rowan , Clitheroe, Crystal-Leigh , Faya, Ngonidzashe , Tastan Bishop, Özlem
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125708 , vital:35810 , https://doi.10.1016/j.bbrc.2014.11.103
- Description: The heat shock organizing protein (Hop) is important in modulating the activity and co-interaction of two chaperones: heat shock protein 70 and 90 (Hsp70 and Hsp90). Recent research suggested that Plasmodium falciparum Hop (PfHop), PfHsp70 and PfHsp90 form a complex in the trophozoite infective stage. However, there has been little computational research on the malarial Hop protein in complex with other malarial Hsps. Using in silico characterization of the protein, this work showed that individual domains of Hop are evolving at different rates within the protein. Differences between human Hop (HsHop) and PfHop were identified by motif analysis. Homology modeling of PfHop and HsHop in complex with their own cytosolic Hsp90 and Hsp70 C-terminal peptide partners indicated excellent conservation of the Hop concave TPR sites bound to the C-terminal motifs of partner proteins. Further, we analyzed additional binding sites between Hop and Hsp90, and showed, for the first time, that they are distinctly less conserved between human and malaria parasite. These sites are located on the convex surface of Hop TPR2, and involved in interactions with the Hsp90 middle domain. Since the convex sites are less conserved than the concave sites, it makes their potential for malarial inhibitor design extremely attractive (as opposed to the concave sites which have been the focus of previous efforts).
- Full Text:
- Date Issued: 2015
- Authors: Hatherley, Rowan , Clitheroe, Crystal-Leigh , Faya, Ngonidzashe , Tastan Bishop, Özlem
- Date: 2015
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125708 , vital:35810 , https://doi.10.1016/j.bbrc.2014.11.103
- Description: The heat shock organizing protein (Hop) is important in modulating the activity and co-interaction of two chaperones: heat shock protein 70 and 90 (Hsp70 and Hsp90). Recent research suggested that Plasmodium falciparum Hop (PfHop), PfHsp70 and PfHsp90 form a complex in the trophozoite infective stage. However, there has been little computational research on the malarial Hop protein in complex with other malarial Hsps. Using in silico characterization of the protein, this work showed that individual domains of Hop are evolving at different rates within the protein. Differences between human Hop (HsHop) and PfHop were identified by motif analysis. Homology modeling of PfHop and HsHop in complex with their own cytosolic Hsp90 and Hsp70 C-terminal peptide partners indicated excellent conservation of the Hop concave TPR sites bound to the C-terminal motifs of partner proteins. Further, we analyzed additional binding sites between Hop and Hsp90, and showed, for the first time, that they are distinctly less conserved between human and malaria parasite. These sites are located on the convex surface of Hop TPR2, and involved in interactions with the Hsp90 middle domain. Since the convex sites are less conserved than the concave sites, it makes their potential for malarial inhibitor design extremely attractive (as opposed to the concave sites which have been the focus of previous efforts).
- Full Text:
- Date Issued: 2015
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
How to establish a bioinformatics postgraduate degree programme—a case study from South Africa
- Machanick, Philip, Tastan Bishop, Özlem
- Authors: Machanick, Philip , Tastan Bishop, Özlem
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124641 , vital:35641 , https://doi.10.1093/bib/bbu014
- Description: The Research Unit in Bioinformatics at Rhodes University (RUBi), South Africa, offers a Masters of Science in Bioinformatics.Growing demand for bioinformatics qualifications results in applications from across Africa.Courses aim to bridge gaps in the diverse backgrounds of students who range from biologists with no prior computing exposure to computer scientists with no biology background. The programme is evenly split between coursework and research, with diverse modules from a range of departments coveringmathematics, statistics, computer science and biology, with emphasis on application to bioinformatics research. The early focus on research helps bring students up to speed with working as a researcher. We measure success of the programme by the high rate of subsequent entry to PhD study: 10 of 14 students who completed in the years 2011-2013.
- Full Text:
- Date Issued: 2014
- Authors: Machanick, Philip , Tastan Bishop, Özlem
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/124641 , vital:35641 , https://doi.10.1093/bib/bbu014
- Description: The Research Unit in Bioinformatics at Rhodes University (RUBi), South Africa, offers a Masters of Science in Bioinformatics.Growing demand for bioinformatics qualifications results in applications from across Africa.Courses aim to bridge gaps in the diverse backgrounds of students who range from biologists with no prior computing exposure to computer scientists with no biology background. The programme is evenly split between coursework and research, with diverse modules from a range of departments coveringmathematics, statistics, computer science and biology, with emphasis on application to bioinformatics research. The early focus on research helps bring students up to speed with working as a researcher. We measure success of the programme by the high rate of subsequent entry to PhD study: 10 of 14 students who completed in the years 2011-2013.
- Full Text:
- Date Issued: 2014
Sequence and domain conservation of the coelacanth Hsp40 and Hsp90 chaperones suggests conservation of function
- Tastan Bishop, Özlem, Edkins, Adrienne L, Blatch, Gregory L
- Authors: Tastan Bishop, Özlem , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126932 , vital:35936 , https://doi.10.1002/jez.b.22541
- Description: Molecular chaperones and their associated co‐chaperones play an important role in preserving and regulating the active conformational state of cellular proteins. The chaperone complement of the Indonesian Coelacanth, Latimeria menadoensis, was elucidated using transcriptomic sequences. Heat shock protein 90 (Hsp90) and heat shock protein 40 (Hsp40) chaperones, and associated cochaperones were focused on, and homologous human sequences were used to search the sequence databases. Coelacanth homologs of the cytosolic, mitochondrial and endoplasmic reticulum (ER) homologs of human Hsp90 were identified, as well as all of the major co‐chaperones of the cytosolic isoform. Most of the human Hsp40s were found to have coelacanth homologs, and the data suggested that all of the chaperone machinery for protein folding at the ribosome, protein translocation to cellular compartments such as the ER and protein degradation were conserved. Some interesting similarities and differences were identified when interrogating human, mouse, and zebrafish homologs. For example, DnaJB13 is predicted to be a non‐functional Hsp40 in humans, mouse, and zebrafish due to a corrupted histidine‐proline‐aspartic acid (HPD) motif, while the coelacanth homolog has an intact HPD. These and other comparisons enabled important functional and evolutionary questions to be posed for future experimental studies.
- Full Text:
- Date Issued: 2014
- Authors: Tastan Bishop, Özlem , Edkins, Adrienne L , Blatch, Gregory L
- Date: 2014
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126932 , vital:35936 , https://doi.10.1002/jez.b.22541
- Description: Molecular chaperones and their associated co‐chaperones play an important role in preserving and regulating the active conformational state of cellular proteins. The chaperone complement of the Indonesian Coelacanth, Latimeria menadoensis, was elucidated using transcriptomic sequences. Heat shock protein 90 (Hsp90) and heat shock protein 40 (Hsp40) chaperones, and associated cochaperones were focused on, and homologous human sequences were used to search the sequence databases. Coelacanth homologs of the cytosolic, mitochondrial and endoplasmic reticulum (ER) homologs of human Hsp90 were identified, as well as all of the major co‐chaperones of the cytosolic isoform. Most of the human Hsp40s were found to have coelacanth homologs, and the data suggested that all of the chaperone machinery for protein folding at the ribosome, protein translocation to cellular compartments such as the ER and protein degradation were conserved. Some interesting similarities and differences were identified when interrogating human, mouse, and zebrafish homologs. For example, DnaJB13 is predicted to be a non‐functional Hsp40 in humans, mouse, and zebrafish due to a corrupted histidine‐proline‐aspartic acid (HPD) motif, while the coelacanth homolog has an intact HPD. These and other comparisons enabled important functional and evolutionary questions to be posed for future experimental studies.
- Full Text:
- Date Issued: 2014
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