2v95
From Proteopedia
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STRUTURE OF CORTICOSTEROID-BINDING GLOBULIN IN COMPLEX WITH CORTISOL
Overview
Corticosteroid-binding globulin (CBG) is a serine proteinase inhibitor, (serpin) family member that transports glucocorticoids in blood and, regulates their access to target cells. The 1.9 A crystal structure of rat, CBG shows that its steroid-binding site resembles the thyroxin-binding, site in the related serpin, thyroxin-binding globulin (TBG), and, mutagenesis studies have confirmed the contributions of key residues that, constitute the steroid-binding pocket. Unlike thyroxin-bound TBG, the, cortisol-bound CBG displays an "active" serpin conformation with the, proteinase-sensitive, reactive centre loop (RCL) fully expelled from the, regulatory beta-sheet A. Moreover, the CBG structure allows us to predict, that complete insertion of the proteolytically cleaved RCL into the serpin, fold occurs in concert with a displacement and unwinding of helix D that, would disrupt the steroid-binding site. This allosteric coupling between, RCL positioning and occupancy of the CBG steroid-binding site, which, resembles the ligand (glycosamino-glycan)-dependant activation of the, thrombin inhibitory serpins heparin cofactor II and anti-thrombin RCLs, ensures both optimal recognition of CBG by target proteinases and, efficient release of steroid to sites of action.
About this Structure
2V95 is a Single protein structure of sequence from Rattus norvegicus with PDN as ligand. This structure superseeds the now removed PDB entry 2V6D. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Corticosteroid-binding globulin: structural basis for steroid transport and proteinase-triggered release., Klieber MA, Underhill C, Hammond GL, Muller YA, J Biol Chem. 2007 Jul 19;. PMID:17644521
Page seeded by OCA on Tue Dec 18 20:32:30 2007
