title: Genome Analysis of Structure-Function Relationships in Respiratory Complex I, an Ancient Bioenergetic Enzyme.
abstract: 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.
authors.affiliation: Italian Institute of Technology, Genova, Italy Center for Genomic Sciences, UNAM, Cuernavaca, Mexico Mauro.DegliEsposti@iit.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Degli Esposti
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D042967:Electron Transport Complex I / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D008969:Molecular Sequence Data
chemical_list: D001426:Bacterial Proteins; D042967:Electron Transport Complex I
keywords: NADH-ubiquinone oxidoreductase; bacterial evolution; mitochondria; respiratory complex I; respiratory inhibitors; ubiquinone