title: Structural characterization of a D-isomer specific 2-hydroxyacid dehydrogenase from Lactobacillus delbrueckii ssp. bulgaricus.
abstract: Hydroxyacid dehydrogenases, responsible for the stereospecific conversion of 2-keto acids to 2-hydroxyacids in lactic acid producing bacteria, have a range of biotechnology applications including antibiotic synthesis, flavor development in dairy products and the production of valuable synthons. The genome of Lactobacillus delbrueckii ssp. bulgaricus, a member of the heterogeneous group of lactic acid bacteria, encodes multiple hydroxyacid dehydrogenases whose structural and functional properties remain poorly characterized. Here, we report the apo and coenzyme NAD⁺ complexed crystal structures of the L. bulgaricusD-isomer specific 2-hydroxyacid dehydrogenase, D2-HDH. Comparison with closely related members of the NAD-dependent dehydrogenase family reveals that whilst the D2-HDH core fold is structurally conserved, the substrate-binding site has a number of non-canonical features that may influence substrate selection and thus dictate the physiological function of the enzyme.
authors.affiliation: EMBL c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany. sjholton@googlemail.com
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Holton
authors.forename: Madhankumar
authors.initials: M
authors.lastname: Anandhakrishnan
authors.forename: Arie
authors.initials: A
authors.lastname: Geerlof
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D007536:Isomerism; D048668:Lactobacillus delbrueckii / Q000201:enzymology*; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D009243:NAD; D000429:Alcohol Oxidoreductases; C083779:2-hydroxyacid dehydrogenase