{PDOC00063} {PS00065; D_2_HYDROXYACID_DH_1} {PS00670; D_2_HYDROXYACID_DH_2} {PS00671; D_2_HYDROXYACID_DH_3} {BEGIN} ************************************************************* * D-isomer specific 2-hydroxyacid dehydrogenases signatures * ************************************************************* A number of NAD-dependent 2-hydroxyacid dehydrogenases which seem to be specific for the D-isomer of their substrate have been shown [1,2,3,4] to be functionally and structurally related. These enzymes are listed below. - D-lactate dehydrogenase (EC 1.1.1.28), a bacterial enzyme which catalyzes the reduction of D-lactate to pyruvate. - D-glycerate dehydrogenase (EC 1.1.1.29) (NADH-dependent hydroxypyruvate reductase), a plant leaf peroxisomal enzyme that catalyzes the reduction of hydroxypyruvate to glycerate. This reaction is part of the glycolate pathway of photorespiration. - D-glycerate dehydrogenase from the bacteria Hyphomicrobium methylovorum and Methylobacterium extorquens. - 3-phosphoglycerate dehydrogenase (EC 1.1.1.95), a bacterial enzyme that catalyzes the oxidation of D-3-phosphoglycerate to 3-phosphohydroxypyruvate. This reaction is the first committed step in the 'phosphorylated' pathway of serine biosynthesis. - Erythronate-4-phosphate dehydrogenase (EC 1.1.1.-) (gene pdxB), a bacterial enzyme involved in the biosynthesis of pyridoxine (vitamin B6). - D-2-hydroxyisocaproate dehydrogenase (EC 1.1.1.-) (D-hicDH), a bacterial enzyme that catalyzes the reversible and stereospecific interconversion between 2-ketocarboxylic acids and D-2-hydroxy-carboxylic acids. - Formate dehydrogenase (EC 1.2.1.2) (FDH) from the bacteria Pseudomonas sp. 101 and various fungi [5]. - Vancomycin resistance protein vanH from Enterococcus faecium; this protein is a D-specific alpha-keto acid dehydrogenase involved in the formation of a peptidoglycan which does not terminate by D-alanine thus preventing vancomycin binding. - Escherichia coli hypothetical protein ycdW. - Escherichia coli hypothetical protein yiaE. - Haemophilus influenzae hypothetical protein HI1556. - Yeast hypothetical protein YER081w. - Yeast hypothetical protein YIL074w. All these enzymes have similar enzymatic activities and are structurally related. We have selected three of the most conserved regions of these proteins to develop patterns. The first pattern is based on a glycine-rich region located in the central section of these enzymes, this region probably corresponds to the NAD-binding domain. The two other patterns contain a number of conserved charged residues, some of which may play a role in the catalytic mechanism. -Consensus pattern: [LIVMA]-[AG]-[IVT]-[LIVMFY]-[AG]-x-G-[NHKRQGSAC]-[LIV]-G- x(13,14)-[LIVMFT]-{A}-x-[FYWCTH]-[DNSTK] -Sequences known to belong to this class detected by the pattern: ALL, except for 5 sequences. -Other sequence(s) detected in Swiss-Prot: 5. -Consensus pattern: [LIVMFYWA]-[LIVFYWC]-x(2)-[SAC]-[DNQHR]-[IVFA]-[LIVF]-x- [LIVF]-[HNI]-x-P-x(4)-[STN]-x(2)-[LIVMF]-x-[GSDN] -Sequences known to belong to this class detected by the pattern: ALL, except for 5 sequences. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: [LMFATCYV]-[KPQNHAR]-x-[GSTDNK]-x-[LIVMFYWRC]- [LIVMFYW](2)-N-x-[STAGC]-R-[GP]-x-[LIVH]-[LIVMCT]-[DNVE] -Sequences known to belong to this class detected by the pattern: ALL, except for 2 sequences. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: Escherichia coli D-lactate dehydrogenase (gene dld) does not belong to this family, it is a membrane-bound FAD flavoenzyme. -Last update: April 2006 / Pattern revised. [ 1] Grant G.A. "A new family of 2-hydroxyacid dehydrogenases." Biochem. Biophys. Res. Commun. 165:1371-1374(1989). PubMed=2692566 [ 2] Kochhar S., Hunziker P.E., Leong-Morgenthaler P., Hottinger H. "Evolutionary relationship of NAD(+)-dependent D-lactate dehydrogenase: comparison of primary structure of 2-hydroxy acid dehydrogenases." Biochem. Biophys. Res. Commun. 184:60-66(1992). PubMed=1567457 [ 3] Taguchi H., Ohta T. "D-lactate dehydrogenase is a member of the D-isomer-specific 2-hydroxyacid dehydrogenase family. Cloning, sequencing, and expression in Escherichia coli of the D-lactate dehydrogenase gene of Lactobacillus plantarum." J. Biol. Chem. 266:12588-12594(1991). PubMed=1840590 [ 4] Goldberg J.D., Yoshida T., Brick P. "Crystal structure of a NAD-dependent D-glycerate dehydrogenase at 2.4 A resolution." J. Mol. Biol. 236:1123-1140(1994). PubMed=8120891 [ 5] Popov V.O., Lamzin V.S. "NAD(+)-dependent formate dehydrogenase." Biochem. J. 301:625-643(1994). PubMed=8053888 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}