2vdy

CRYSTAL STRUCTURE OF THE REACTIVE LOOP CLEAVED CORTICOSTEROID BINDING GLOBULIN COMPLEXED WITH CORTISOL

spinqualitylabelsall models 2vdy, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vdy is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HCY Related: 2vdx Resources: FirstGlance, OCA, RCSB, PDBsum Disease [CBG_HUMAN] Corticosteroid-binding globulin deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function [CBG_HUMAN] Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species. 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 Corticosteroids are transported in the blood by a serpin, corticosteroid-binding globulin (CBG), and their normally equilibrated release can be further triggered by the cleavage of the reactive loop of CBG. We report here the crystal structures of cleaved human CBG (cCBG) at 1.8-A resolution and its complex with cortisol at 2.3-A resolution. As expected, on cleavage, CBG undergoes the irreversible S-to-R serpin transition, with the cleaved reactive loops being fully incorporated into the central beta-sheet. A connecting loop of helix D, which is in a helix-like conformation in native CBG, unwinds and grossly perturbs the hormone binding site following beta-sheet expansion in the cCBG structure but shifts away from the binding site by more than 8 A following the binding of cortisol. Unexpectedly, on cortisol binding, the hormone binding site of cCBG adopts a configuration almost identical with that of the native conformer. We conclude that CBG has adapted an allosteric mechanism of the serpins to allow equilibrated release of the hormones by a flip-flop movement of the intact reactive loop into and out of the beta-sheet. The change in the hormone binding affinity results from a change in the flexibility or plasticity of the connecting loop, which modulates the configuration of the binding site. The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release.,Zhou A, Wei Z, Stanley PL, Read RJ, Stein PE, Carrell RW J Mol Biol. 2008 Jun 27;380(1):244-51. Epub 2008 May 14. PMID:18513745 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Corticosteroid-binding globulin

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