title: The crystal structure of D-mandelate dehydrogenase reveals its distinct substrate and coenzyme recognition mechanisms from those of 2-ketopantoate reductase.
abstract: D-Mandelate dehydrogenases (D-ManDHs), belonging to a new d-2-hydroxyacid dehydrogenase family, catalyze the conversion between benzoylformate and d-mandelate using NAD as a coenzyme. We determined the first D-ManDH structure, that of ManDH2 from Enterococcus faecalis IAM10071. The overall structure showed ManDH2 has a similar fold to 2-ketopantoate reductase (KPR), which catalyzes the conversion of 2-ketopantoate to d-pantoate using NADP as a coenzyme. They share conserved catalytic residues, indicating ManDH2 has the same reaction mechanism as KPR. However, ManDH2 exhibits significant structural variations in the coenzyme and substrate binding sites compared to KPR. These structural observations could explain their different coenzyme and substrate specificities.
authors: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: miyanaga.a.aa@m.titech.ac.jp.
authors: Akimasa
authors: A
authors: Miyanaga
authors: Shinsuke
authors: S
authors: Fujisawa
authors: Nayuta
authors: N
authors: Furukawa
authors: Kazuhito
authors: K
authors: Arai
authors: Masahiro
authors: M
authors: Nakajima
authors: Hayao
authors: H
authors: Taguchi
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D003067:Coenzymes / Q000737:chemistry; D013293:Enterococcus faecalis / Q000201:enzymology*; D004926:Escherichia coli / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D003067:Coenzymes; D011994:Recombinant Proteins; D000429:Alcohol Oxidoreductases; C043630:D-mandelate dehydrogenase; C021934:2-dehydropantoate 2-reductase
keywords: 2-Ketopantoate reductase; 2-ketopantoate reductase; 2-ketopantoate reductase from Escherichia coli; CENDH; Coenzyme specificity; Crystal structure; EcKPR; KPR; ManDH2; N-(1-d-carboxyethyl)-l-norvaline dehydrogenase from Arthrobacter sp.; Substrate specificity; d-2-HydDH; d-2-hydroxyacid dehydrogenase; d-ManDH; d-Mandelate dehydrogenase; d-mandelate dehydrogenase; d-mandelate dehydrogenase from Enterococcus faecalis IAM10071; rmsd; root mean square deviation.