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2vdx
From Proteopedia
| 2vdx, resolution 1.84Å () | |||||||||
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| Sites: | , , and | ||||||||
| Ligands: | |||||||||
| Related: | 2vdy | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
CRYSTAL STRUCTURE OF THE REACTIVE LOOP CLEAVED CORTICOSTEROID BINDING GLOBULIN
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.
About this Structure
2VDX is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Zhou A, Wei Z, Stanley PL, Read RJ, Stein PE, Carrell RW. The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release. J Mol Biol. 2008 Jun 27;380(1):244-51. Epub 2008 May 14. PMID:18513745 doi:10.1016/j.jmb.2008.05.012
Page seeded by OCA on Mon Feb 16 22:15:25 2009
