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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2013.08.019 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The ternary complex structure of d-mandelate dehydrogenase with NADH and anilino(oxo)acetate.
Biochem Biophys Res Commun
May 2017
Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address:
Enterococcus faecium NAD-dependent d-mandelate dehydrogenase (d-ManDH) belongs to a ketopantoate reductase (KPR)-related d-2-hydroxyacid dehydrogenase family, and exhibits broad substrate specificity toward bulky hydrophobic 2-ketoacids, preferring C3-branched substrates. The ternary complex structure of d-ManDH with NADH and anilino(oxo)acetate (AOA) revealed that the substrate binding induces a shear motion of the N-terminal domain along the C-terminal domain, following the hinge motion induced by the NADH binding, and allows the bound NADH molecule to form favorable interactions with a 2-ketoacid substrate. d-ManDH possesses a sufficiently wide pocket that accommodates the C3 branched side chains of substrates like KPR, but unlike the pocket of KPR, the pocket of d-ManDH comprises an entirely hydrophobic surface and an expanded space, in which the AOA benzene is accommodated.
View Article and Find Full Text PDFThe crystal structure of D-mandelate dehydrogenase reveals its distinct substrate and coenzyme recognition mechanisms from those of 2-ketopantoate reductase.
Biochem Biophys Res Commun
September 2013
Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address:
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.
View Article and Find Full Text PDFStructural insights into the enzyme mechanism of a new family of d-2-hydroxyacid dehydrogenases, a close homolog of 2-ketopantoate reductase.
Genome Inform
October 2009
National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki-shi, Osaka 567-0085, Japan.
A newly identified family of NAD-dependent D-2-hydroxyacid dehydrogenases (D-2-HydDHs) catalyzes the stereo-specific reduction of branched-chain 2-keto acids with bulky hydrophobic side chains to 2-hydroxyacids. They are promising targets for industrial/practical applications, particularly in the stereo-specific synthesis of C3-branched D-hydroxyacids. Comparative modeling and docking studies have been performed to build models of the enzyme-cofactor-substrate complexes and identify key residues for cofactor and substrate recognition.
View Article and Find Full Text PDFThe D-2-hydroxyacid dehydrogenase incorrectly annotated PanE is the sole reduction system for branched-chain 2-keto acids in Lactococcus lactis.
J Bacteriol
February 2009
INRA, UR 477 Biochimie Bactérienne, F-78350 Jouy-en-Josas, France.
Hydroxyacid dehydrogenases of lactic acid bacteria, which catalyze the stereospecific reduction of branched-chain 2-keto acids to 2-hydroxyacids, are of interest in a variety of fields, including cheese flavor formation via amino acid catabolism. In this study, we used both targeted and random mutagenesis to identify the genes responsible for the reduction of 2-keto acids derived from amino acids in Lactococcus lactis. The gene panE, whose inactivation suppressed hydroxyisocaproate dehydrogenase activity, was cloned and overexpressed in Escherichia coli, and the recombinant His-tagged fusion protein was purified and characterized.
View Article and Find Full Text PDFA new family of D-2-hydroxyacid dehydrogenases that comprises D-mandelate dehydrogenases and 2-ketopantoate reductases.
Biosci Biotechnol Biochem
April 2008
Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
The gene for the D-mandelate dehydrogenase (D-ManDH) of Enterococcus faecalis IAM10071 was isolated by means of an activity staining procedure and PCR and expressed in Escherichia coli cells. The recombinant enzyme exhibited high catalytic activity toward various 2-ketoacid substrates with bulky hydrophobic side chains, particularly C3-branched substrates such as benzoylformate and 2-ketoisovalerate, and strict coenzyme specificity for NADH and NAD(+). It showed marked sequence similarity with known NADP-dependent 2-ketopantoate reductases (KPR).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!