1cwb
From Proteopedia
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|PDB= 1cwb |SIZE=350|CAPTION= <scene name='initialview01'>1cwb</scene>, resolution 2.2Å | |PDB= 1cwb |SIZE=350|CAPTION= <scene name='initialview01'>1cwb</scene>, resolution 2.2Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DMT:3-HYDROXY-4,4-DIMETHYL-2-(METHYLAMINO)-6-OCTENOIC+ACID'>DMT</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= CYCLOPHILIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CYCLOPHILIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1cwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cwb OCA], [http://www.ebi.ac.uk/pdbsum/1cwb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1cwb RCSB]</span> | ||
}} | }} | ||
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[[Category: complex (isomerase/immunosuppressant)]] | [[Category: complex (isomerase/immunosuppressant)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:29:46 2008'' |
Revision as of 16:29, 30 March 2008
| |||||||
| , resolution 2.2Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , | ||||||
| Gene: | CYCLOPHILIN (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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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