Binding region of alanopine dehydrogenase predicted by unbiased molecular dynamics simulations of ligand diffusion.
Opine dehydrogenases catalyze the reductive condensation of pyruvate with L-amino acids. Biochemical characterization of alanopine dehydrogenase from Arenicola marina revealed that this enzyme is highly specific for L-alanine. Unbiased molecular dynamics simulations with a homology model of alanopine dehydrogenase captured the binding of L-alanine diffusing from solvent to a putative binding region near a distinct helix-kink-helix motif. These results and sequence comparisons reveal how mutations and insertions within this motif dictate the L-amino acid specificity.
Institute for Pharmaceutical and Medicinal Chemistry and ‡Institute of Biochemistry, Department of Mathematics and Natural Sciences, Heinrich-Heine-University , 40204 Düsseldorf, Germany.
Holger
H
Gohlke
Ulrike
U
Hergert
Tatu
T
Meyer
Daniel
D
Mulnaes
Manfred K
MK
Grieshaber
Sander H J
SH
Smits
Lutz
L
Schmitt
D000409:Alanine / Q000737:chemistry* / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D004058:Diffusion; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011077:Polychaeta / Q000737:chemistry* / Q000201:enzymology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019289:Pyruvic Acid / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein; D013379:Substrate Specificity
D015801:Helminth Proteins; D008024:Ligands; D011994:Recombinant Proteins; D019289:Pyruvic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; C030014:alanopine dehydrogenase; D000409:Alanine