1m63: Difference between revisions

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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="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1m63, resolution 2.80Å" />

'''Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes'''<br />

==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.

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==

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==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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1M63 OCA].

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==

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[[Category: Huai, Q.]]

[[Category: Ke, H.]]

[[Category: Kim, H.Y.]]

[[Category: Kim, H Y.]]

[[Category: Liu, J.O.]]

[[Category: Liu, J O.]]

[[Category: Liu, Y.]]

[[Category: Mondragon, A.]]

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[[Category: immunophilin]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 18~~:08:~~00 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:55 2008''

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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="450" color="white" frame="true" align="right" spinBox="true"
 caption="1m63, resolution 2.80&Aring;" />
 '''Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes'''<br />
 ==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.
+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==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-M63 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1M63 OCA].
+M63 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==
@@ Line 20: / Line 19: @@
 [[Category: Huai, Q.]]
 [[Category: Ke, H.]]
-[[Category: Kim, H.Y.]]
+[[Category: Kim, H Y.]]
-[[Category: Liu, J.O.]]
+[[Category: Liu, J O.]]
 [[Category: Liu, Y.]]
 [[Category: Mondragon, A.]]
@@ Line 32: / Line 31: @@
 [[Category: immunophilin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:08:00 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:55 2008''