2v95
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Corticosteroid-binding globulin (CBG) is a serine proteinase inhibitor | + | 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 1.9A crystal structure of rat CBG shows that its steroid-binding site resembles the thyroxin-binding site in the related serpin, thyroxin-binding globulin, and mutagenesis studies have confirmed the contributions of key residues that constitute the steroid-binding pocket. Unlike thyroxin-bound thyroxin-binding globulin, the cortisol-bound CBG displays an "active" serpin conformation with the proteinase-sensitive, reactive center 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)-dependent 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== | ==About this Structure== | ||
| - | 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 <scene name='pdbligand=PDN:'>PDN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 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 <scene name='pdbligand=PDN:'>PDN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 2V6D. Known structural/functional Site: <scene name='pdbsite=AC1:Pdn+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V95 OCA]. |
==Reference== | ==Reference== | ||
| - | Corticosteroid-binding globulin | + | Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release., Klieber MA, Underhill C, Hammond GL, Muller YA, J Biol Chem. 2007 Oct 5;282(40):29594-603. Epub 2007 Jul 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17644521 17644521] |
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Klieber, M | + | [[Category: Klieber, M A.]] |
| - | [[Category: Muller, Y | + | [[Category: Muller, Y A.]] |
[[Category: PDN]] | [[Category: PDN]] | ||
[[Category: cbg]] | [[Category: cbg]] | ||
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[[Category: transport]] | [[Category: transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:54:15 2008'' |
Revision as of 16:54, 21 February 2008
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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 1.9A crystal structure of rat CBG shows that its steroid-binding site resembles the thyroxin-binding site in the related serpin, thyroxin-binding globulin, and mutagenesis studies have confirmed the contributions of key residues that constitute the steroid-binding pocket. Unlike thyroxin-bound thyroxin-binding globulin, the cortisol-bound CBG displays an "active" serpin conformation with the proteinase-sensitive, reactive center 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)-dependent 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 as ligand. This structure supersedes the now removed PDB entry 2V6D. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release., Klieber MA, Underhill C, Hammond GL, Muller YA, J Biol Chem. 2007 Oct 5;282(40):29594-603. Epub 2007 Jul 19. PMID:17644521
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