1ynd

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{{STRUCTURE_1ynd| PDB=1ynd | SCENE= }}
{{STRUCTURE_1ynd| PDB=1ynd | SCENE= }}
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'''Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6A resolution'''
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===Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6A resolution===
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==Overview==
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Sanglifehrin A (SFA) is a novel immunosuppressant isolated from Streptomyces sp. that binds strongly to the human immunophilin cyclophilin A (CypA). SFA exerts its immunosuppressive activity through a mode of action different from that of all other known immunophilin-binding substances, namely cyclosporine A (CsA), FK506, and rapamycin. We have determined the crystal structure of human CypA in complex with SFA at 1.6 A resolution. The high resolution of the structure revealed the absolute configuration at all 17 chiral centers of SFA as well as the details of the CypA/SFA interactions. In particular, it was shown that the 22-membered macrocycle of SFA is deeply embedded in the same binding site as CsA and forms six direct hydrogen bonds with CypA. The effector domain of SFA, on the other hand, has a chemical and three-dimensional structure very different from CsA, already strongly suggesting different immunosuppressive mechanisms. Furthermore, two CypA.SFA complexes form a dimer in the crystal as well as in solution as shown by light scattering and size exclusion chromatography experiments. This observation raises the possibility that the dimer of CypA.SFA complexes is the molecular species mediating the immunosuppressive effect.
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{{ABSTRACT_PUBMED_15772070}}
==About this Structure==
==About this Structure==
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[[Category: Isomerase]]
[[Category: Isomerase]]
[[Category: Rotamase]]
[[Category: Rotamase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:32:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:05:21 2008''

Revision as of 11:05, 28 July 2008

Template:STRUCTURE 1ynd

Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6A resolution

Template:ABSTRACT PUBMED 15772070

About this Structure

1YND is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6 A resolution., Kallen J, Sedrani R, Zenke G, Wagner J, J Biol Chem. 2005 Jun 10;280(23):21965-71. Epub 2005 Mar 16. PMID:15772070

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