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首页> 外文期刊>Biochemistry >X-ray Crystal Structure of Bovine 3 Glu-Osteocalcin
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X-ray Crystal Structure of Bovine 3 Glu-Osteocalcin

机译：牛3 Glu-骨钙蛋白的X射线晶体结构

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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 ? 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.
机译：在低维生素K摄入或口服抗凝剂（华法令）期间，血清钙蛋白的3 Glu形式（3 Glu-OCN）会增加。以前使用圆二色性的报告显示，它的结构比3 Gla Ca2 +-骨钙素少，并且与骨矿物质的结合力不强。最近的研究表明，3 Glu-OCN作为葡萄糖代谢的潜在调节剂。在胰腺和睾丸中发现的G蛋白偶联受体GPRC6a被确定为假定的骨钙素受体。这项研究的目的是使用X射线晶体学确定牛3 Glu-OCN的高分辨率结构，以了解与矿物质和GPRC6a受体的分子相互作用。生长热脱羧的牛骨钙素的衍射质量晶体，并且晶体结构确定为1.88λ。解析度。最终的精制结构包含残基17-47，并且像3 Gla Ca2 + -OCN一样，由围绕疏水核的三个α-螺旋组成，两个螺旋之间存在C23-C29二硫键，并且没有结合的Ca2 +。因此，3 Glu-OCN的螺旋结构是不依赖Ca2 +的，但类似于3 Gla Ca2 + -OCN的螺旋结构。 3 Glu-OCN上较少的Ca2 +配位体可能导致矿物结合水平降低。该结构表明，GPRC6a受体可能对螺旋骨钙素有反应，并将有助于提供分子机制，了解3 Glu-OCN在葡萄糖稳态中的作用。

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