From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2rmb.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:2rmb.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2rmb| PDB=2rmb | SCENE= }} | | {{STRUCTURE_2rmb| PDB=2rmb | SCENE= }} |
| | | | |
| - | '''CRYSTAL STRUCTURES OF CYCLOPHILIN A COMPLEXED WITH CYCLOSPORIN A AND N-METHYL-4-[(E)-2-BUTENYL]-4,4-DIMETHYLTHREONINE CYCLOSPORIN A'''
| + | ===CRYSTAL STRUCTURES OF CYCLOPHILIN A COMPLEXED WITH CYCLOSPORIN A AND N-METHYL-4-[(E)-2-BUTENYL]-4,4-DIMETHYLTHREONINE CYCLOSPORIN A=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | BACKGROUND: Cyclophilin (CyP) is a ubiquitious intracellular protein that binds the immunosuppressive drug cyclosporin A (CsA). CyP-CsA forms a ternary complex with calcineurin and thereby inhibits T-cell activation. CyP also has enzymatic activity, catalyzing the cis-trans isomerization of peptidyl-prolyl amide bonds. RESULTS: We have determined the structure of human cyclophilin A (CyPA) complexed with CsA to 2.1 A resolution. We also report here the structure of CyPA complexed with an analog of CsA, CsA (MeBm2t1-CsA), which binds less well to CyPA, but has increased immunosuppressive activity. Comparison of these structures with previously determined structures of unligated CyPA and CyPA complexed with a candidate substrate for the isomerase activity, the dipeptide AlaPro, reveals that subtle conformational changes occur in both CsA and CyPA on complex formation. CONCLUSIONS: MeBm2t1-CsA binds to CyPA in an essentially similar manner to CsA. The 100-fold weaker affinity of its binding may be attributable to the close contact between MeBmt1 and the active site residue Ala103 of CyPA, which causes small conformational changes in both protein and drug. One change, the slight movement of MeLeu6 in CsA relative to MeBm2t1-CsA, may be at least partially responsible for the higher affinity of the CyPA-MeBm2t1-CsA complex for calcineurin. Our comparison between CyPA-CsA and CyPA-AlaPro suggests that CsA is probably not an analog of the natural substrate, confirming that the catalytic activity of CyPA is not related to its role in immunosuppression either structurally or functionally.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8075981}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8075981 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_8075981}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 25: |
Line 29: |
| | [[Category: Ke, H.]] | | [[Category: Ke, H.]] |
| | [[Category: Mayrose, D.]] | | [[Category: Mayrose, D.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:09:52 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 17:16:50 2008'' |
Revision as of 14:16, 27 July 2008
Template:STRUCTURE 2rmb
CRYSTAL STRUCTURES OF CYCLOPHILIN A COMPLEXED WITH CYCLOSPORIN A AND N-METHYL-4-[(E)-2-BUTENYL]-4,4-DIMETHYLTHREONINE CYCLOSPORIN A
Template:ABSTRACT PUBMED 8075981
About this Structure
2RMB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of cyclophilin A complexed with cyclosporin A and N-methyl-4-[(E)-2-butenyl]-4,4-dimethylthreonine cyclosporin A., Ke H, Mayrose D, Belshaw PJ, Alberg DG, Schreiber SL, Chang ZY, Etzkorn FA, Ho S, Walsh CT, Structure. 1994 Jan 15;2(1):33-44. PMID:8075981
Page seeded by OCA on Sun Jul 27 17:16:50 2008
