Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. II. Environment of bound NADPH and implications for catalysis.

摘要: New details of NADPH binding to Lactobacillus casei dihydrofolate reductase have become visible as a result crystallographic refinement an R factor 0.152 at 1.7 A resolution. Conformational torsion angles for bound been extensively revised and specific interatomic contacts responsible cofactor identified. In addition, several structurally conserved water molecules are seen mediate the protein-ligand interaction. nicotinamide site three oxygen atoms enzyme lie in plane pyridine ring close carbons 2, 4, 6. The placement these polar groups suggests that stabilizes C4-carbonium electronic isomer oxidized transition state. Pyramidalization nitrogen N1 state might be promoted by fixed molecule positioned donate hydrogen bond lone pair orbital. could also relieve unfavorable steric contact due observed rotation nicotinamide's carboxamide group 180 degrees from its most stable conformation.