Publication Abstract from PubMed
The electron distribution in the coenzyme-substrate adduct of aspartate aminotransferase was changed by replacing active-site Arg386 with alanine and introducing a new arginine residue nearby. [Y225R, R386A]Aspartate aminotransferase decarboxylates L-aspartate to L-alanine (kcat = 0.04 s-1), while its transaminase activity towards dicarboxylic amino acids is decreased by three orders of magnitude (kcat = 0.19 s-1). Molecular-dynamics simulations based on the crystal structure of the mutant enzyme suggest that a new hydrogen bond to the imine N atom of the pyridoxal-5'-phosphate- aspartate adduct and an altered electrostatic potential around its beta-carboxylate group underlie the 650,000-fold increase in the ratio of beta-decarboxylase/transaminase activity.
Changing the reaction specificity of a pyridoxal-5'-phosphate-dependent enzyme.,Graber R, Kasper P, Malashkevich VN, Sandmeier E, Berger P, Gehring H, Jansonius JN, Christen P Eur J Biochem. 1995 Sep 1;232(2):686-90. PMID:7556224[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
