据介绍，双胍类药物（包括广泛用于治疗糖尿病的药物二甲双胍）的分子作用模式尚未完全确定。
研究人员通过结合冷冻电镜和酶动力学来定义模型双胍与哺乳动物呼吸复合物I的抑制药物和相关靶点的相互作用。研究人员解释这些数据是为了解释双胍与不同酶状态结合的选择性。主要抑制位点位于醌结合通道的两亲性区域，另外一个结合位点位于酶膜间隙一侧的一个口袋中。一种独立的局部离液相互作用，以前没有任何药物描述过，取代了膜结构域中的一部分关键螺旋。
总之，这一数据为双胍的作用提供了结构基础，并使药用双胍的合理设计成为可能。
附：英文原文
Title: Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides
Author: Hannah R. Bridges, James N. Blaza, Zhan Yin, Injae Chung, Michael N. Pollak, Judy Hirst
Issue&Volume: 2023-01-27
Abstract: The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo–electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides.
DOI: ade3332
Source: https://www.science.org/doi/10.1126/science.ade3332