title: Phylogenetic analyses of proton-translocating transhydrogenases.
abstract: The proton-translocating nicotinamide nucleotide transhydrogenases (TH) provide a simple model for understanding chemically coupled transmembrane proton translocation. To further our understanding of TH structure-function relationships, we have identified all sequenced homologous of these vectorial enzymes and have conducted sequence comparison studies. The NAD-binding domains of TH are homologous to bacterial alanine dehydrogenases (ADH) and eukaryotic saccharopine dehydrogenases (SDH) as well as N5(carboxyethyl)-L-ornithine synthase of Lactococcus lactis and dipicolinate synthase of Bacillus subtilis. A multiple alignment, a phylogenetic tree, and two signature sequences for this family, designated the TH-ADH-SDH or TAS superfamily, have been derived. Additionally, the TH family has been characterized. Phylogenetic analyses suggested that these proteins have evolved without inter-system shuffling. However, interdomain splicing-fusion events have occurred during the evolution of several of these systems. Analyses of the multiple alignment for the TH family revealed that domain conservation occurs in the order: NADP-binding domain (domain III) > NAD-binding domain (domain I) > proton-translocating transmembrane domain (domain II). A topologic model for the proton-translocating transmembrane domain consistent with published data is presented, and a possible involvement of specific transmembrane alpha-helical segments in channel formation is suggested.
authors.affiliation: Department of Biology, University of California at San Diego, La Jolla, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Studley
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hatefi
authors.forename: M H
authors.initials: MH
authors.lastname: Saier
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D001692:Biological Transport; D005057:Eukaryotic Cells; D008969:Molecular Sequence Data; D009250:NADP Transhydrogenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D011522:Protons; D012443:Saccharopine Dehydrogenases / Q000235:genetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D011522:Protons; D000594:Amino Acid Oxidoreductases; D012443:Saccharopine Dehydrogenases; D009250:NADP Transhydrogenases