2cpl
From Proteopedia
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SIMILARITIES AND DIFFERENCES BETWEEN HUMAN CYCLOPHILIN A AND OTHER BETA-BARREL STRUCTURES. STRUCTURAL REFINEMENT AT 1.63 ANGSTROMS RESOLUTION
Overview
The structure of the unligated recombinant human cyclophilin A (CyP A) has, been refined to an R-factor of 0.18 at 1.63 A resolution. The, root-mean-squared deviations of the refined structure are 0.013 A and 2.50, degrees from ideal geometries of bond length and bond angle, respectively., Eight antiparallel beta-strands of CyP A form a right-handed beta-barrel., The structure of CyP A is compared with other members in the antiparallel, eight-stranded beta-barrel family and with the parallel eight-stranded, alpha/beta barrels. Although all known eight-stranded barrels are, right-handed, the tilted angle of the strands against the barrel axis, varies from 45 degrees for retinol binding protein and 49 degrees for CyP, A to 70 degrees for superoxide dismutase. As a result, the beta-barrel of, CyP A is not completely superimposable with other members of beta-barrels., The structure of CyP A has a unique topology, distinct from other members, in the beta-barrel family. In addition, CyP A is a closed beta-barrel so, that neither the immunosuppressive drug cyclosporin A (CsA) nor the, proline-containing substrate can bind to the hydrophobic core of the CyP A, barrel, while the hydrophobic core of most other barrels is open for, ligation. These observations probably indicate that CyP A is neither, functionally nor evolutionally related to other beta-barrel structures., Details of interactions between solvent molecules and the active site, residues of CyP A are illustrated. A water-co-operated mechanism, where, the cis<-->trans isomerization might possibly consist of (1) transition of, the prolyl bond and (2) release of N or C-terminal residues of substrate, from CyP, is addressed. The refined structure reveals no disulfide bridges, in CyP A. Cys115 is near the CsA site, but unlikely to be directly, involved in CsA binding because of steric hindrance from Thr119 and, Leu122. This geometry probably rules out any mechanisms involving a, tetrahedral intermediate formed between cysteine and substrate during, cis<-->trans isomerization.
About this Structure
2CPL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63 A resolution., Ke H, J Mol Biol. 1992 Nov 20;228(2):539-50. PMID:1453463
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