title: Nicotinoprotein (NAD+ -containing) alcohol dehydrogenase: structural relationships and functional interpretations.
abstract: The primary structure of nicotinoprotein alcohol dehydrogenase (ADH) from Amycolatopsis methanolica was determined and used for modelling against known ADH structures, and for evaluation of the coenzyme binding. The results establish the medium-chain dehydrogenase/reductase nature of the nicotinoprotein ADH. Its subunit model and that of the human class Ibeta ADH subunit structure are similar, with mean a carbon deviations of 0.95 A, but they differ in seven loops. Nicotinoprotein ADH occupies a phylogenetic position intermediate between the dimeric and tetrameric ADH families. Two of the differing loops are important for coenzyme binding in the nicotinoprotein model, where one (with a Thr271Arg exchange towards the traditional enzyme) may suggest a slight rotation of the coenzyme adenine ring in the nicotinoprotein, and the other, with an Asn288 insertion, may suggest an extra hydrogen bond to its nicotinamide ribose, favouring stronger binding of the coenzyme. Combined with previous data, this suggests differences in the details of the tight coenzyme binding in different nicotinoproteins, but a common mode for this binding by loop differences.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Norin
authors.forename: S R
authors.initials: SR
authors.lastname: Piersma
authors.forename: J A
authors.initials: JA
authors.lastname: Duine
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000192:Actinomycetales / Q000201:enzymology*; D000426:Alcohol Dehydrogenase / Q000737:chemistry* / Q000502:physiology; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D000426:Alcohol Dehydrogenase