2v95: Difference between revisions

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.

2V95 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with PDN as [http://en.wikipedia.org/wiki/ligand ligand]. This structure superseeds the now removed PDB entry 2V6D. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2V95 OCA].  

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