Degli Esposti Mauro
Italian Institute of Technology, Genova, Italy Center for Genomic Sciences, UNAM, Cuernavaca, Mexico
Genome Biol Evol. 2015 Nov 27;8(1):126-47. doi: 10.1093/gbe/evv239.
Respiratory complex I (NADH:ubiquinone oxidoreductase) is a ubiquitous bioenergetic enzyme formed by over 40 subunits in eukaryotes and a minimum of 11 subunits in bacteria. Recently, crystal structures have greatly advanced our knowledge of complex I but have not clarified the details of its reaction with ubiquinone (Q). This reaction is essential for bioenergy production and takes place in a large cavity embedded within a conserved module that is homologous to the catalytic core of Ni-Fe hydrogenases. However, how a hydrogenase core has evolved into the protonmotive Q reductase module of complex I has remained unclear. This work has exploited the abundant genomic information that is currently available to deduce structure-function relationships in complex I that indicate the evolutionary steps of Q reactivity and its adaptation to natural Q substrates. The results provide answers to fundamental questions regarding various aspects of complex I reaction with Q and help re-defining the old concept that this reaction may involve two Q or inhibitor sites. The re-definition leads to a simplified classification of the plethora of complex I inhibitors while throwing a new light on the evolution of the enzyme function.
呼吸链复合体I（NADH：泛醌氧化还原酶）是一种普遍存在的生物能量酶，在真核生物中由40多个亚基组成，在细菌中至少由11个亚基组成。最近，晶体结构极大地推进了我们对复合体I的认识，但尚未阐明其与泛醌（Q）反应的细节。该反应对于生物能量产生至关重要，发生在一个嵌入保守模块的大腔中，该模块与镍铁氢化酶的催化核心同源。然而，氢化酶核心如何进化为复合体I的质子动力Q还原酶模块仍不清楚。这项工作利用了目前可用的丰富基因组信息来推断复合体I中的结构-功能关系，这些关系表明了Q反应性的进化步骤及其对天然Q底物的适应性。结果为关于复合体I与Q反应各个方面的基本问题提供了答案，并有助于重新定义这一反应可能涉及两个Q或抑制剂位点的旧概念。这种重新定义导致了对大量复合体I抑制剂的简化分类，同时为酶功能的进化提供了新的视角。
