Structural insights into the broadened substrate profile of the extended-spectrum β-lactamase OXY-1-1 from Klebsiella oxytoca

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 R₁ and R₂ 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.