Liu, Beibei published the artcileConformational Dynamics-Guided Loop Engineering of an Alcohol Dehydrogenase: Capture, Turnover and Enantioselective Transformation of Difficult-to-Reduce Ketones, Recommanded Product: Picolinonitrile, the main research area is conformation dynamics engineering alc dehydrogenase enantioselective transformation difficult ketone.
Directed evolution of enzymes for the asym. reduction of prochiral ketones to produce enantio-pure secondary alcs. is particularly attractive in organic synthesis. Loops located at the active pocket of enzymes often participate in conformational changes required to fine-tune residues for substrate binding and catalysis. It is therefore of great interest to control the substrate specificity and stereochem. of enzymic reactions by manipulating the conformational dynamics. Herein, a secondary alc. dehydrogenase was chosen to enantioselectively catalyze the transformation of difficult-to-reduce bulky ketones, which are not accepted by the wildtype enzyme. Guided by previous work and particularly by structural anal. and mol. dynamics (MD) simulations, two key residues alanine 85 (A85) and isoleucine 86 (I86) situated at the binding pocket were thought to increase the fluctuation of a loop region, thereby yielding a larger volume of the binding pocket to accommodate bulky substrates. Subsequently, site-directed saturation mutagenesis was performed at the two sites. The best mutant, where residue alanine 85 was mutated to glycine and isoleucine 86 to leucine (A85G/I86L), can efficiently reduce bulky ketones to the corresponding pharmaceutically interesting alcs. with high enantioselectivities (∼99% ee). Taken together, this study demonstrates that introducing appropriate mutations at key residues can induce a higher flexibility of the active site loop, resulting in the improvement of substrate specificity and enantioselectivity.
Advanced Synthesis & Catalysis published new progress about Conformational transition. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, Recommanded Product: Picolinonitrile.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts