8번째 carboxylesterase family에 속하는 EstU1의 beta-lactamase 활성에 대한 구조기반 연구

Abstract

EstU1 is a remarkable family VIII carboxylesterase in that it exhibits hydrolytic activity towards the amide bond of clinically-used &#61538 beta-lactam antibiotics as well as the ester bond of p-nitrophenyl esters. To reveal the structural basis for the catalytic feature, we determined the crystal structures of EstU1 and the EstU1/cephalothin complex. EstU1 assumes a two-domain structure consisting of a helical domain and a &#61537 /&#61538 domain. This &#61538 beta-lactamase-like modular architecture, together with the fact that Ser100, Lys103, and Tyr218 in EstU1 is definitely matched with the three catalytic residues (Ser64, Lys67, and Tyr150) of class C &#61538 beta-lactamases, is compatible with the &#61538 beta-lactamase activity of EstU1. basis for the catalytic feature, we determined the crystal structures of EstU1 and the EstU1/cephalothin complex. EstU1 assumes a two-domain structure consisting of a helical domain and a &#61537 /&#61538 domain. This &#61538 beta-lactamase-like modular architecture, together with the fact that Ser100, Lys103, and Tyr218 in EstU1 is definitely matched with the three catalytic residues (Ser64, Lys67, and Tyr150) of class C &#61538 beta-lactamases, is compatible with the &#61538 beta-lactamase activity of EstU1.