1cwb

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

spinqualitylabelsall models 1cwb, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1cwb is a 2 chain structure with sequence from Homo sapiens and Tolypocladium inflatum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: ABA, DAL, DMT, MLE, MVA, SAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PPIA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cyclophilin 3D structures

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