| Structural highlights
1cwb is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | NonStd Res: | , , , , , |
| Related: | 1bck, 1c5f, 1csa, 1cwa, 1cwc, 1cwf, 1cwh, 1cwi, 1cwj, 1cwk, 1cwl, 1cwm, 1cwo, 1cya, 1cyb, 1cyn, 1ikf, 1m63, 1mf8, 1mik, 1qng, 1qnh, 1xq7, 2esl, 2oju, 2poy, 2rma, 2rmb, 2rmc, 2wfj, 2x2c, 2x7k, 2z6w, 3bo7, 3cys, 3eov |
| Gene: | CYCLOPHILIN (HUMAN) |
| Activity: | Peptidylprolyl isomerase, with EC number 5.2.1.8 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mikol V, Kallen J, Walkinshaw MD. The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity. Protein Eng. 1994 May;7(5):597-603. PMID:8073029
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