1m63 | pdb_00001m63

Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes

spinqualitylabelsall models 1m63, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1m63 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, FE, ZN NonStd Res: ABA, BMT, DAL, MLE, MVA, SAR Related: 1bck, 1c5f, 1csa, 1cwa, 1cwb, 1cwc, 1cwf, 1cwh, 1cwi, 1cwj, 1cwk, 1cwl, 1cwm, 1cwo, 1cya, 1cyb, 1cyn, 1ikf, 1mf8, 1mik, 1qng, 1qnh, 1xq7, 2esl, 2oju, 2poy, 2rma, 2rmb, 2rmc, 2wfj, 2x2c, 2x7k, 2z6w, 3bo7, 3cys, 3eov Gene: CNA ALPHA (HUMAN), CNB (HUMAN) Activity: Phosphoprotein phosphatase, with EC number 3.1.3.16 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PP2BA_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1. [PPIA_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. [CANB1_HUMAN] Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity. 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 Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the common target for two immunophilin-immunosuppressant complexes, cyclophilin A-cyclosporin A (CyPA-CsA) and FKBP-FK506. How the two structurally distinct immunophilin-drug complexes bind the same target has remained unknown. We report the crystal structure of calcineurin (CN) in complex with CyPA-CsA at 2.8-A resolution. The CyPA-CsA complex binds to a composite surface formed by the catalytic and regulatory subunits of CN, where the complex of FK506 and its binding protein FKBP also binds. While the majority of the CN residues involved in the binding are common for both immunophilin-immunosuppressant complexes, a significant number of the residues are distinct. Unlike FKBP-FK506, CyPA-CsA interacts with Arg-122 at the active site of CN, implying direct involvement of CyPA-CsA in the regulation of CN catalysis. The simultaneous interaction of CyPA with both the composite surface and the active site of CN suggests that the composite surface may serve as a substrate recognition site responsible for the narrow substrate specificity of CN. The comparison of CyPA-CsA-CN with FKBP-FK506-CN significantly contributes to understanding the molecular basis of regulation of CN activity by the immunophilin-immunosuppressant. Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes.,Huai Q, Kim HY, Liu Y, Zhao Y, Mondragon A, Liu JO, Ke H Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12037-42. Epub 2002 Sep 6. PMID:12218175 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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