1m63

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{{STRUCTURE_1m63| PDB=1m63 | SCENE= }}
{{STRUCTURE_1m63| PDB=1m63 | SCENE= }}
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'''Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes'''
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===Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes===
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==Overview==
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Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the common target for two immunophilin-immunosuppressant complexes, cyclophilin A-cyclosporin A (CyPA-CsA) and FKBP-FK506. How the two structurally distinct immunophilin-drug complexes bind the same target has remained unknown. We report the crystal structure of calcineurin (CN) in complex with CyPA-CsA at 2.8-A resolution. The CyPA-CsA complex binds to a composite surface formed by the catalytic and regulatory subunits of CN, where the complex of FK506 and its binding protein FKBP also binds. While the majority of the CN residues involved in the binding are common for both immunophilin-immunosuppressant complexes, a significant number of the residues are distinct. Unlike FKBP-FK506, CyPA-CsA interacts with Arg-122 at the active site of CN, implying direct involvement of CyPA-CsA in the regulation of CN catalysis. The simultaneous interaction of CyPA with both the composite surface and the active site of CN suggests that the composite surface may serve as a substrate recognition site responsible for the narrow substrate specificity of CN. The comparison of CyPA-CsA-CN with FKBP-FK506-CN significantly contributes to understanding the molecular basis of regulation of CN activity by the immunophilin-immunosuppressant.
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(as it appears on PubMed at http://www.pubmed.gov), where 12218175 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12218175}}
==About this Structure==
==About this Structure==
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[[Category: Crystal structure]]
[[Category: Crystal structure]]
[[Category: Immunophilin]]
[[Category: Immunophilin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:40:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:17:45 2008''

Revision as of 20:17, 2 July 2008

Image:1m63.png

Template:STRUCTURE 1m63

Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes

Template:ABSTRACT PUBMED 12218175

About this Structure

1M63 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes., Huai Q, Kim HY, Liu Y, Zhao Y, Mondragon A, Liu JO, Ke H, Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12037-42. Epub 2002 Sep 6. PMID:12218175

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