Paper Citing NAMD - Abstract
Docquier, Jean-Denis; Calderone, Vito; De Luca, Filomena; Benvenuti, Manuela; Giuliani, Francesco; Bellucci, Luca; Tafi, Andrea; Nordmann, Patrice; Botta, Maurizio; Rossolini, Gian Maria; Mangani, Stefano
Crystal Structure of the OXA-48 beta-Lactamase Reveals Mechanistic Diversity among Class D Carbapenemases
CHEMISTRY & BIOLOGY, 16:540-547, MAY 29 2009
Carbapenem-hydrolyzing class D beta-lactamases (CHDLs) are enzymes found in important Gram-negative pathogens (mainly Acinetobacter baumannii and Enterobacteriaceae) that confer resistance to beta-lactam antibiotics, and notably carbapenems. The crystal structure of the OXA-48 carbapenemase was determined at pH 7.5 and at a resolution of 1.9 angstrom. Surprisingly, and by contrast with OXA-24, the only other CHDL of known crystal structure, the structure of OXA-48 was similar to OXA-10, an enzyme devoid of carbapenemase activity, indicating that the hydrolysis of these compounds could depend on subtle changes in the active site region. Moreover, the active site groove of OXA-48 was different from that of OXA-24 in shape, dimensions, and charge distribution. Molecular dynamics pointed to the functional relevance of residues located in or close to the beta 5-beta 6 loop and allowed us to propose a mechanism for carbapenem hydrolysis by OXA-48.
