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4MZZ

Crystal structure of Bovine 3 Glu-Osteocalcin.

Summary for 4MZZ
Entry DOI10.2210/pdb4mzz/pdb
DescriptorOsteocalcin (2 entities in total)
Functional Keywordsstructural genomics, protein structure initiative, nysgrc, psi-biology, new york structural genomics research consortium, structural protein
Biological sourceBos taurus (bovine,cow,domestic cattle,domestic cow)
Cellular locationSecreted: P02820
Total number of polymer chains2
Total formula weight7804.61
Authors
Malashkevich, V.N.,Dowd, T.L.,Almo, S.C.,New York Structural Genomics Research Consortium (NYSGRC) (deposition date: 2013-09-30, release date: 2013-11-27, Last modification date: 2024-11-27)
Primary citationMalashkevich, V.N.,Almo, S.C.,Dowd, T.L.
X-ray crystal structure of bovine 3 Glu-osteocalcin.
Biochemistry, 52:8387-8392, 2013
Cited by
PubMed Abstract: The 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 Ca²⁺-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 Å resolution. The final refined structure contained residues 17-47 and, like 3 Gla Ca²⁺-OCN, consisted of three α-helices surrounding a hydrophobic core, a C23-C29 disulfide bond between two of the helices, and no bound Ca²⁺. Thus, the helical structure of 3 Glu-OCN is Ca²⁺-independent but similar to that of 3 Gla Ca²⁺-OCN. A reduced level of mineral binding could result from a lower number of Ca²⁺ 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.
PubMed: 24138653
DOI: 10.1021/bi4010254
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.88 Å)
Structure validation

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