1cwb: Difference between revisions

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[[Image:1cwb.gif|left|200px]]
{{Seed}}
[[Image:1cwb.png|left|200px]]


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{{STRUCTURE_1cwb|  PDB=1cwb  |  SCENE=  }}  
{{STRUCTURE_1cwb|  PDB=1cwb  |  SCENE=  }}  


'''THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY'''
===THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY===




==Overview==
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For most of the cyclosporin A (CsA) analogs, there is generally a good correlation between cyclophilin binding and immunosuppression. However, this relationship does not seem to hold for 4-[(E)-2-butenyl]-4,4,N-trimethyl-L-threonine1 (MeBm2t)1-CsA. Its affinity for cyclophilin was reported to be approximately 1% that of CsA and its immunosuppressive activity in vitro was shown to be approximately 30% that of CsA. We report here the crystal structure of a complex between recombinant human cyclophilin A (CypA) and (MeBm2t)1-CsA which has been determined by X-ray crystallography at 2.2 A resolution and refined to an R-factor of 16.3%. (MeBm2t)1-CsA shows a similar bound conformation and network of interactions to CypA as CsA. The measured lower affinity for CypA cannot therefore be explained by a different mode of binding. We propose that the poor affinity to CypA could be accounted for by the existence of an equilibrium in aqueous solution between a 'cyclophilin bound conformation' and a 'non-binding conformation' of (MeBm2t)1-CsA. The relatively high immunosuppressive activity is suggested to result from slight conformational differences observed in the effector domain.
The line below this paragraph, {{ABSTRACT_PUBMED_8073029}}, adds the Publication Abstract to the page
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{{ABSTRACT_PUBMED_8073029}}


==About this Structure==
==About this Structure==
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[[Category: Mikol, V.]]
[[Category: Mikol, V.]]
[[Category: Walkinshaw, M D.]]
[[Category: Walkinshaw, M D.]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 13:11:00 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 21:37:18 2008''

Revision as of 18:37, 30 June 2008

File:1cwb.png

Template:STRUCTURE 1cwb

THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY

Template:ABSTRACT PUBMED 8073029

About this Structure

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

Reference

The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity., Mikol V, Kallen J, Walkinshaw MD, Protein Eng. 1994 May;7(5):597-603. PMID:8073029

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