人钙结合型S100A1的X射线晶体结构
X-ray crystal structure of human calcium-bound S100A1.
作者信息
Melville Zephan, Aligholizadeh Ehson, McKnight Laura E, Weber Dylan J, Pozharski Edwin, Weber David J
机构信息
Center for Biomolecular Therapeutics, Department of Biochemistry and Molecular Biology, University of Maryland Baltimore, 108 North Greene Street, Baltimore, MD 21201, USA.
出版信息
Acta Crystallogr F Struct Biol Commun. 2017 Apr 1;73(Pt 4):215-221. doi: 10.1107/S2053230X17003983. Epub 2017 Mar 22.
Abstract
S100A1 is a member of the S100 family of Ca-binding proteins and regulates several cellular processes, including those involved in Ca signaling and cardiac and skeletal muscle function. In Alzheimer's disease, brain S100A1 is overexpressed and gives rise to disease pathologies, making it a potential therapeutic target. The 2.25 Å resolution crystal structure of Ca-S100A1 is solved here and is compared with the structures of other S100 proteins, most notably S100B, which is a highly homologous S100-family member that is implicated in the progression of malignant melanoma. The observed structural differences in S100A1 versus S100B provide insights regarding target protein-binding specificity and for targeting these two S100 proteins in human diseases using structure-based drug-design approaches.
摘要
S100A1是钙结合蛋白S100家族的成员，可调节多种细胞过程，包括参与钙信号传导以及心脏和骨骼肌功能的过程。在阿尔茨海默病中，脑S100A1过度表达并引发疾病病理，使其成为潜在的治疗靶点。本文解析了Ca-S100A1分辨率为2.25 Å的晶体结构，并与其他S100蛋白的结构进行了比较，最显著的是S100B，它是S100家族中高度同源的成员，与恶性黑色素瘤的进展有关。观察到的S100A1与S100B之间的结构差异为靶蛋白结合特异性以及使用基于结构的药物设计方法在人类疾病中靶向这两种S100蛋白提供了见解。
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