Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Division of Functional Structure, Department of Morphological Biology, Fukuoka Dental College, Fukuoka, Japan.
FEBS Lett. 2023 Jun;597(11):1479-1488. doi: 10.1002/1873-3468.14618. Epub 2023 Apr 4.
An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose metabolism. Here, we describe the high-resolution X-ray crystal structure of decarboxylated osteocalcin under acidic conditions. Decarboxylated osteocalcin at pH 2.0 retains the α-helix structure of native osteocalcin with three γ-carboxyglutamic acid residues at neutral pH. This implies that decarboxylated osteocalcin is stable under an acidic environment in bone. In addition, site-directed mutagenesis revealed that Glu17 and Glu21 are important for the adiponectin-inducing activity of decarboxylated osteocalcin. These findings suggest that the receptor of decarboxylated osteocalcin responds to the negative charge in helix 1 of osteocalcin.
骨组织中的酸性环境对于骨代谢和去羧化骨钙素的产生至关重要，后者作为葡萄糖代谢的调节激素发挥作用。在这里，我们描述了酸性条件下去羧化骨钙素的高分辨率 X 射线晶体结构。在 pH 值为 2.0 时，去羧化骨钙素保留了天然骨钙素的α-螺旋结构，其中三个γ-羧基谷氨酸残基处于中性 pH 值。这意味着去羧化骨钙素在骨组织的酸性环境中是稳定的。此外，定点突变揭示了 Glu17 和 Glu21 对于去羧化骨钙素的脂联素诱导活性很重要。这些发现表明，去羧化骨钙素的受体对骨钙素螺旋 1 中的负电荷作出反应。
