2v95

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Structure of Corticosteroid-Binding Globulin in complex with CortisolStructure of Corticosteroid-Binding Globulin in complex with Cortisol

Structural highlights

2v95 is a 1 chain structure with sequence from Rattus norvegicus. This structure supersedes the now removed PDB entry 2v6d. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.93Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CBG_RAT Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.[1]

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

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.

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[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Klieber MA, Underhill C, Hammond GL, Muller YA. Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release. J Biol Chem. 2007 Oct 5;282(40):29594-603. Epub 2007 Jul 19. PMID:17644521 doi:10.1074/jbc.M705014200
  2. Klieber MA, Underhill C, Hammond GL, Muller YA. Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release. J Biol Chem. 2007 Oct 5;282(40):29594-603. Epub 2007 Jul 19. PMID:17644521 doi:10.1074/jbc.M705014200

2v95, resolution 1.93Å

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