西奈山团队绘出AASS酶完整结构：为罕见遗传病戊二酸尿症1型的药物设计提供新线索
西奈山伊坎医学院的研究团队11月13日宣布，已绘出人体 AASS 酶的首个详细完整结构。AASS 的全称是α-氨基己二酸半醛合酶，负责分解氨基酸赖氨酸。这一成果发表于11月13日上线的《科学进展》（Science Advances），研究结合了冷冻电子显微镜、生化实验与计算机模拟。
研究人员在这种酶上发现了一处类似铰链的柔性调控区域，细微变化就能显著改变酶的活性。这一发现与戊二酸尿症1型（GA1）直接相关：这是一种遗传性代谢疾病，患者体内有毒物质蓄积，可能造成不可逆的脑损伤。摸清 AASS 的结构与调控方式，为设计能够调节其活性的药物分子提供了起点。
研究团队同时强调，这只是实验室阶段的早期一步，距离真正的治疗方法还很远，下一步是设计抑制剂分子。这项研究由美国国立卫生研究院下属机构支持，论文资深作者包括 Michael B. Lazarus、Sander M. Houten 与 Robert J. DeVita。（来源：西奈山医疗系统）
Mount Sinai Team Maps the AASS Enzyme in Full, Offering New Clues for Treating the Rare Genetic Disease Glutaric Aciduria Type 1
Researchers at the Icahn School of Medicine at Mount Sinai announced on November 13 that they have produced the first detailed, complete structure of the human AASS enzyme, which breaks down the amino acid lysine. The work, published in the November 13 online issue of Science Advances, combined cryo-electron microscopy, biochemical experiments and computer simulations.
The team identified a flexible, hinge-like regulatory region of the enzyme where small changes can substantially alter its activity. The finding matters for glutaric aciduria type 1 (GA1), an inherited metabolic disorder in which toxic substances build up in the body and can cause irreversible brain damage. Understanding how AASS is built and regulated gives drug designers a starting point for molecules that could adjust its activity.
The researchers stress that this is an early, laboratory-stage step, not a treatment or a cure; the next step is designing inhibitor molecules. The study was supported by the National Institutes of Health, and its senior and co-corresponding authors include Michael B. Lazarus, Sander M. Houten and Robert J. DeVita. (Source: Mount Sinai)
来源：西奈山医疗系统
发布：GSM·美国（发布链接）
图片来源：图片来源：Wikimedia Commons「Mount Sinai Hospital (55494328982).jpg」（Ajay Suresh 摄，CC BY 4.0），图中为位于纽约的西奈山医院建筑群 Image: Wikimedia Commons "Mount Sinai Hospital (55494328982).jpg" (by Ajay Suresh, CC BY 4.0), The Mount Sinai Hospital complex in New York
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