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 we 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 these 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.
Baker
M E
ME
Department of Medicine, University of California, San Diego 92093-0823, USA. mbaker@ucsd.edu
Grundy
W N
WN
Elkan
C P
CP
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D002417:Cattle; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D016946:Gram-Negative Aerobic Rods and Cocci / Q000201:enzymology / Q000235:genetics; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics; D008390:Markov Chains; D008969:Molecular Sequence Data; D005810:Multigene Family; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000235:genetics*; D009492:Neurospora crassa / Q000201:enzymology / Q000235:genetics; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software
D001426:Bacterial Proteins; D005656:Fungal Proteins; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases; D016660:NAD(P)H Dehydrogenase (Quinone)