蛋白質-リガンド複合体構造と相互作用の解析

抄録

Complex structures of neocarzinostatin (NCS) and β-lactamase/β-lactam antibiotics were built using NMR and crystallographic data of the proteins. On binding of ligands to proteins, particular amino acid side chains as well as ligands show dynamic character to exhibit specific molecular recognition. NMR studies and conformational analysis of the Phe 78 side chain of NCS revealed that the Phe 78 residue plays a major role on the chromophore binding through conformational change of the side chain aromatic moiety. Crystal structures and computational modeling of the enzyme-ligand complexes indicated that at the active site, the carboxylate of β-lactam antibiotics induces the conformational change of the Lys 73 residue and acts as a trigger of the hydrolytic reaction (acylation). Modeling of the acyl-enzyme structures also suggested the role of a mobile water molecule at the active site for deacylation. Experimental (NMR and X-ray crystallography) and computational results provided a fruitful information about molecular interaction between proteins and ligands.