1m63
From Proteopedia
(New page: 200px<br /> <applet load="1m63" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m63, resolution 2.80Å" /> '''Crystal structure o...) |
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| - | [[Image:1m63.gif|left|200px]]<br /> | + | [[Image:1m63.gif|left|200px]]<br /><applet load="1m63" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1m63" size=" | + | |
caption="1m63, resolution 2.80Å" /> | caption="1m63, resolution 2.80Å" /> | ||
'''Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes'''<br /> | '''Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1M63 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA, ZN and FE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] Full crystallographic information is available from [http:// | + | 1M63 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=FE:'>FE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M63 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Huai, Q.]] | [[Category: Huai, Q.]] | ||
[[Category: Ke, H.]] | [[Category: Ke, H.]] | ||
| - | [[Category: Kim, H | + | [[Category: Kim, H Y.]] |
| - | [[Category: Liu, J | + | [[Category: Liu, J O.]] |
[[Category: Liu, Y.]] | [[Category: Liu, Y.]] | ||
[[Category: Mondragon, A.]] | [[Category: Mondragon, A.]] | ||
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[[Category: immunophilin]] | [[Category: immunophilin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:55 2008'' |
Revision as of 11:51, 21 February 2008
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Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Cornea plana congenita, recessive OMIM:[603288], Myotonic dystrophy, type 2 OMIM:[116955]
About this Structure
1M63 is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Active as Phosphoprotein phosphatase, with EC number 3.1.3.16 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
Page seeded by OCA on Thu Feb 21 13:51:55 2008
Categories: Homo sapiens | Phosphoprotein phosphatase | Protein complex | Huai, Q. | Ke, H. | Kim, H Y. | Liu, J O. | Liu, Y. | Mondragon, A. | Zhao, Y. | CA | FE | ZN | Calcineurin | Crystal structure | Immunophilin
