Structural Characterization of Carbonic Anhydrase VIII and Effects of Missense Single Nucleotide Variations to Protein Structure and Function:
- Sanyanga, Taremekedzwa Allan, Tastan Bishop, Özlem
- Authors: Sanyanga, Taremekedzwa Allan , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149670 , vital:38873 , https://doi.org/10.3390/ijms21082764
- Description: Human carbonic anhydrase 8 (CA-VIII) is an acatalytic isoform of the α -CA family. Though the protein cannot hydrate CO2, CA-VIII is essential for calcium (Ca2+) homeostasis within the body, and achieves this by allosterically inhibiting the binding of inositol 1,4,5-triphosphate (IP3) to the IP3 receptor type 1 (ITPR1) protein. However, the mechanism of interaction of CA-VIII to ITPR1 is not well understood. In addition, functional defects to CA-VIII due to non-synonymous single nucleotide polymorphisms (nsSNVs) result in Ca2+ dysregulation and the development of the phenotypes such as cerebellar ataxia, mental retardation and disequilibrium syndrome 3 (CAMRQ3). The pathogenesis of CAMRQ3 is also not well understood. The structure and function of CA-VIII was characterised, and pathogenesis of CAMRQ3 investigated. Structural and functional characterisation of CA-VIII was conducted through SiteMap and CPORT to identify potential binding site residues.
- Full Text:
- Authors: Sanyanga, Taremekedzwa Allan , Tastan Bishop, Özlem
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/149670 , vital:38873 , https://doi.org/10.3390/ijms21082764
- Description: Human carbonic anhydrase 8 (CA-VIII) is an acatalytic isoform of the α -CA family. Though the protein cannot hydrate CO2, CA-VIII is essential for calcium (Ca2+) homeostasis within the body, and achieves this by allosterically inhibiting the binding of inositol 1,4,5-triphosphate (IP3) to the IP3 receptor type 1 (ITPR1) protein. However, the mechanism of interaction of CA-VIII to ITPR1 is not well understood. In addition, functional defects to CA-VIII due to non-synonymous single nucleotide polymorphisms (nsSNVs) result in Ca2+ dysregulation and the development of the phenotypes such as cerebellar ataxia, mental retardation and disequilibrium syndrome 3 (CAMRQ3). The pathogenesis of CAMRQ3 is also not well understood. The structure and function of CA-VIII was characterised, and pathogenesis of CAMRQ3 investigated. Structural and functional characterisation of CA-VIII was conducted through SiteMap and CPORT to identify potential binding site residues.
- Full Text:
Hepatitis C and HIV Coinfection in Developing Countries:
- Authors: Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/148228 , vital:38721 , ISBN 9780128032343 , https://books.google.co.za/books?id=XSmlCgAAQBAJanddq=hepatitis+c+in+developing+countriesandsource=gbs_navlinks_s
- Description: Because of the common routes of transmission, hepatitis C virus (HCV) coinfection with HIV is frequent. Of the 36.6 million HIV-infected individuals worldwide, about 25% are also coinfected with HCV. Developing countries face the greatest burden of coinfection. HIV infection has been shown to have a significant impact on the progression of chronic HCV, with a higher risk of cirrhosis and hepatocellular carcinoma (HCC). Because of the improvements in the management and treatment of HIV/AIDS in resource-limited countries, HCV/HIV coinfection is becoming a significant clinical problem and a major cause of morbidity and mortality. HCV/HIV coinfection is characterized by aggressive hepatic fibrogenesis, incidence of cirrhosis, and HCC. HCC is currently a major cause for liver-related deaths in HIV patients. Viral eradication has been difficult to attain with interferon and ribavirin therapies. Novel therapies with direct-acting antiviral agents have been promising for this population. However, access to such expensive regimen is far beyond the capabilities of most resource-limited countries. Yet, studies lag behind those for HCV monoinfection.
- Full Text:
- Authors: Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/148228 , vital:38721 , ISBN 9780128032343 , https://books.google.co.za/books?id=XSmlCgAAQBAJanddq=hepatitis+c+in+developing+countriesandsource=gbs_navlinks_s
- Description: Because of the common routes of transmission, hepatitis C virus (HCV) coinfection with HIV is frequent. Of the 36.6 million HIV-infected individuals worldwide, about 25% are also coinfected with HCV. Developing countries face the greatest burden of coinfection. HIV infection has been shown to have a significant impact on the progression of chronic HCV, with a higher risk of cirrhosis and hepatocellular carcinoma (HCC). Because of the improvements in the management and treatment of HIV/AIDS in resource-limited countries, HCV/HIV coinfection is becoming a significant clinical problem and a major cause of morbidity and mortality. HCV/HIV coinfection is characterized by aggressive hepatic fibrogenesis, incidence of cirrhosis, and HCC. HCC is currently a major cause for liver-related deaths in HIV patients. Viral eradication has been difficult to attain with interferon and ribavirin therapies. Novel therapies with direct-acting antiviral agents have been promising for this population. However, access to such expensive regimen is far beyond the capabilities of most resource-limited countries. Yet, studies lag behind those for HCV monoinfection.
- Full Text:
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:
- 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:
- «
- ‹
- 1
- ›
- »