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