A common ancestor for a subunit in the mitochondrial proton-translocating NADH:ubiquinone oxidoreductase (complex I) and short-chain dehydrogenases/reductases

The proton-translocating NADH:ubiquinone oxidoreductase or complex I is located in the inner membranes of mitochondria, where it catalyzes the transfer of electrons from NADH to ubiquinone. Here wt report that one of the subunits in complex I is homologous to short-chain dehydrogenases and reductases? a family of enzymes with diverse activities that include metabolizing steroids, prostaglandins and nucleotide sugars. We discovered that a subunit of complex I in human, cow. Neurospora crassa and Aquifex aeolius is homologous to nucleotide-sugar epimerases and hydroxysteroid dehydrogenases while seeking distant homologs of those enzymes with a hidden Markov model-based search of Genpept. This homology allows us to use information from the solved three-dimensional structures of nucleotide-sugar epimerases and hydroxysteroid dehydrogenases and our motif analysis of these enzymes to predict functional domains on their homologs in complex I.