Structural highlights
Function[OSTCN_BOVIN] Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium. Publication Abstract from PubMedThe 3 Glu form of osteocalcin (3 Glu-OCN) is increased in serum during low vitamin K intake or oral anticoagulant use (warfarin). Previous reports using circular dichroism show it is less structured than 3 Gla Ca(2)(+)-osteocalcin and does not bind strongly to bone mineral. Recent studies have suggested a role for 3 Glu-OCN as a potential regulator of glucose metabolism. A G-protein-coupled receptor, GPRC6a, found in the pancreas and testes was identified as the putative osteocalcin receptor. The purpose of this study is to determine the high-resolution structure of bovine 3 Glu-OCN, using X-ray crystallography, to understand molecular interactions with mineral and the GPRC6a receptor. Diffraction quality crystals of thermally decarboxylated bovine osteocalcin were grown, and the crystal structure was determined to 1.88 A resolution. The final refined structure contained residues 17-47 and, like 3 Gla Ca(2)(+)-OCN, consisted of three alpha-helices surrounding a hydrophobic core, a C23-C29 disulfide bond between two of the helices, and no bound Ca(2)(+). Thus, the helical structure of 3 Glu-OCN is Ca(2)(+)-independent but similar to that of 3 Gla Ca(2)(+)-OCN. A reduced level of mineral binding could result from a lower number of Ca(2)(+) coordinating ligands on 3 Glu-OCN. The structure suggests the GPRC6a receptor may respond to helical osteocalcin and will aid in providing molecular mechanistic insight into the role of 3 Glu-OCN in glucose homeostasis. X-ray crystal structure of bovine 3 Glu-osteocalcin.,Malashkevich VN, Almo SC, Dowd TL Biochemistry. 2013 Nov 26;52(47):8387-92. doi: 10.1021/bi4010254. Epub 2013 Nov, 12. PMID:24138653[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
This page was last modified 08:12, 10 April 2019.