title: Structural basis for the β-lactamase activity of EstU1, a family VIII carboxylesterase.
abstract: EstU1 is a unique family VIII carboxylesterase that displays hydrolytic activity toward the amide bond of clinically used β-lactam antibiotics as well as the ester bond of p-nitrophenyl esters. EstU1 assumes a β-lactamase-like modular architecture and contains the residues Ser100, Lys103, and Tyr218, which correspond to the three catalytic residues (Ser64, Lys67, and Tyr150, respectively) of class C β-lactamases. The structure of the EstU1/cephalothin complex demonstrates that the active site of EstU1 is not ideally tailored to perform an efficient deacylation reaction during the hydrolysis of β-lactam antibiotics. This result explains the weak β-lactamase activity of EstU1 compared with class C β-lactamases. Finally, structural and sequential comparison of EstU1 with other family VIII carboxylesterases elucidates an operative molecular strategy used by family VIII carboxylesterases to extend their substrate spectrum.
authors.affiliation: Marine Biotechnology Research Division, Korea Institute of Ocean Science and Technology, Ansan, 426-744, Republic of Korea; Ocean Science and Technology School, Korea Maritime University, Pusan, 606-791, Republic of Korea; Department of Marine Biotechnology, University of Science and Technology, Daejeon, 305-333, Republic of Korea.
authors.forename: Sun-Shin
authors.initials: SS
authors.lastname: Cha
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: An
authors.forename: Chang-Sook
authors.initials: CS
authors.lastname: Jeong
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Kim
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Jeon
authors.forename: Chang-Muk
authors.initials: CM
authors.lastname: Lee
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Kang
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Lee
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D043182:Carboxylesterase / Q000737:chemistry* / Q000378:metabolism*; D002512:Cephalothin / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D043182:Carboxylesterase; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D002512:Cephalothin
keywords: EstU1; crystal structure of EstU1; crystal structure of the EstU1/cephalothin complex; family VIII carboxylesterases; β-lactamase activity