| Crystal structures of cyclophilin and its partners. | |
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MedLine Citation:
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PMID: 15353287 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cyclophilin (CyP) is a cytosolic receptor of immunosuppressive drug cyclosporin A (CsA). The binary complex of CyP-CsA inhibits the activity of Ca2+/calmodulin dependent serine/threonine calcineurin (CN). The inhibition of CN in turn disables the transcription activity of nuclear factor of activated T cell, thus suppressing the T cell activation and cardiac hypertrophy. CyP is also an enzyme catalyzing peptidyl-prolyl cis-trans isomerization and serves as a molecular chaperone in various biological processes. For example, CyPA is involved in the assembly/deassembly of HIV-1 virion and is required for the full infectious activity of HIV-1. However, the in vivo function of CyP remains a mystery. This review will describe the three-dimensional structures of CyPs and its partners and discuss the structural clues to understanding the CyP functions in biological processes. The structures of CyP in complex with proline-containing peptides provided insight into the mechanism of peptidyl-prolyl cis-trans isomerization. The structures of CyPA in complex with HIV-1 capsid protein and its peptides revealed details of interactions of CyP with HIV-1 capsid protein, thus providing a guideline for design of anti-HIV drugs. The rearrangement of two tetratricopeptide repeats of the, large, cyclophilin CyP40 into a long helix under the crystallization conditions might be biologically relevant to the CyP40 function in the hsp90 molecular chaperone system. The structures of the binary CyPA-CsA and ternary CN-CyPA-CsA complexes showed how CsA binds to its receptors and therefore provide a template for design of new immunosuppressive drugs. |
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Authors:
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Hengming Ke; Qing Huai |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Review Date: 2004-09-01 |
Journal Detail:
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Title: Frontiers in bioscience : a journal and virtual library Volume: 9 ISSN: 1093-4715 ISO Abbreviation: Front. Biosci. Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-09-08 Completed Date: 2006-09-28 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9709506 Medline TA: Front Biosci Country: United States |
Other Details:
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Languages: eng Pagination: 2285-96 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599-7260, USA. hke@med.unc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Capsid Proteins / chemistry Catalysis Crystallography, X-Ray Cyclophilins / chemistry* Cyclosporine / pharmacology Cytosol / metabolism HIV-1 / metabolism Humans Immunosuppressive Agents / pharmacology Peptides / chemistry Protein Binding Protein Conformation Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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GM59791/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Capsid Proteins; 0/Immunosuppressive Agents; 0/Peptides; 59865-13-3/Cyclosporine; EC 5.2.1.-/Cyclophilins |
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