title: Structural insights into the broadened substrate profile of the extended-spectrum β-lactamase OXY-1-1 from Klebsiella oxytoca.
abstract: Klebsiella oxytoca is a pathogen that causes serious infections in hospital patients. It shows resistance to many clinically used β-lactam antibiotics by producing chromosomally encoded OXY-family β-lactamases. Here, the crystal structure of an OXY-family β-lactamase, OXY-1-1, determined at 1.93 Å resolution is reported. The structure shows that the OXY-1-1 β-lactamase has a typical class A β-lactamase fold and exhibits greater similarity to CTX-M-type β-lactamases than to TEM-family or SHV-family β-lactamases. It is also shown that the enzyme provides more space around the active cavity for the R(1) and R(2) substituents of β-lactam antibiotics. The half-positive/half-negative distribution of surface electrostatic potential in the substrate-binding pocket indicates the preferred properties of substrates or inhibitors of the enzyme. The results reported here provide a structural basis for the broadened substrate profile of the OXY-family β-lactamases.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research and Biodynamic Optical Imaging Center (BIOPIC), Peking University, Beijing 100871, People's Republic of China. liangyh@pku.edu.cn
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Liang
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Su
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology*; D041121:Klebsiella oxytoca / Q000737:chemistry* / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001618:beta-Lactamases