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Alcohol Dehydrogenase Dynamics and Catalysis
Author(s) -
Plapp Bryce V.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.609.2
Subject(s) - chemistry , ternary complex , alcohol dehydrogenase , hydride , conformational change , catalysis , active site , nicotinamide , cofactor , enzyme , stereochemistry , enzyme catalysis , protein structure , biophysics , crystallography , biochemistry , organic chemistry , biology , hydrogen
The catalytic mechanism of horse liver alcohol dehydrogenase has been extensively studied. The enzyme changes conformation when coenzyme and substrates bind. Release of a proton from the catalytic zinc‐water via the proton relay system controls the conformational change and suggest that changes in the coordination of the zinc are involved in substrate binding. Substitutions of various amino acid residues in the active site activate the enzyme by increasing the rate‐limiting release of coenzyme product and affect the conformational change, but the rates of hydride transfer decrease modestly. The hydride ion is transferred with quantum mechanical tunneling, implying that the reacting substrates move closer together at the transition state. The contribution of protein motions is being assessed with studies of various mutated forms of the enzyme. High resolution X‐ray crystallography shows that the reduced nicotinamide ring is puckered in ternary complexes with NADH. X‐ray data can also provide information on protein motions that are correlated with the hydride transfer. Protein dynamics are important for catalysis by liver alcohol dehydrogenase. (Supported by grants from NSF and NIH)