Genome Analysis of Structure-Function Relationships in Respiratory Complex I, an Ancient Bioenergetic Enzyme.
Genome Analysis of Structure-Function Relationships in Respiratory Complex I, an Ancient Bioenergetic Enzyme.
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DOI：
10.1093/gbe/evv239
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发表时间：
2015-11-27
影响因子：
3.3
通讯作者：
Degli Esposti M
中科院分区：
文献类型：
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作者：
Degli Esposti M
呼吸复合物I（NADH：泛醌氧化还原酶）是一种普遍存在的生物能酶，在真核生物中由超过40个亚基形成，在细菌中至少有11个亚基。最近，晶体结构大大推进了我们对复合物I的认识，但还没有澄清它与泛醌（Q）反应的细节。该反应对于生物能源生产是必不可少的，并且发生在嵌入保守模块内的大空腔中，该保守模块与Ni-Fe氢化酶的催化核心同源。然而，氢化酶核心如何演变成复合物I的质子动力Q还原酶模块仍不清楚。这项工作利用了丰富的基因组信息，是目前可推断的结构-功能关系，在复杂的I，表明进化步骤的Q反应性和它的适应自然Q基板。结果提供了答案的基本问题，关于各个方面的复杂的I反应与Q和帮助重新定义的旧概念，这种反应可能涉及两个Q或抑制剂的网站。重新定义导致了复杂的I抑制剂过多的一个简化的分类，同时抛出一个新的光的酶功能的演变。
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.