The ternary complex structure of d-mandelate dehydrogenase with NADH and anilino(oxo)acetate.
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. The expanded space mostly comprises a mobile loop structure, which likely modulates the shape and size of the space depending on the substrate.
Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Nayuta
N
Furukawa
Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, Japan.
Akimasa
A
Miyanaga
Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Masahiro
M
Nakajima
Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: htaguchi@rs.noda.tus.ac.jp.
Hayao
H
Taguchi
D000085:Acetates / Q000737:chemistry*; D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000814:Aniline Compounds / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D016984:Enterococcus faecium / Q000737:chemistry* / Q000201:enzymology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity; D013816:Thermodynamics
D000085:Acetates; D000814:Aniline Compounds; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D009243:NAD; D000429:Alcohol Oxidoreductases; C043630:D-mandelate dehydrogenase
2-Ketopantoate reductase; Crystal structure; Domain motion; Substrate specificity; d-mandelate dehydrogenase