4bb2

Crystal structure of cleaved corticosteroid-binding globulin in complex with progesterone

spinqualitylabelsall models 4bb2, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bb2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.48Å Ligands: CYS, EDO, STR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CBG_HUMAN Corticosteroid-binding globulin deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function CBG_HUMAN Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species. Publication Abstract from PubMed Corticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 A crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of beta-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species. Corticosteroid-binding globulin: structure-function implications from species differences.,Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. PMID:23300763 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Corticosteroid-binding globulin

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