Crystal structure of Enterobacter cloacae 908R class C beta-lactamase bound to iodo-acetamido-phenyl boronic acid, a transition-state analogue.
The structures of the class C beta-lactamase from Enterobacter cloacae 908R alone and in complex with a boronic acid transition-state analogue were determined by X-ray crystallography at 2.1 and 2.3 A, respectively. The structure of the enzyme resembles those of other class C beta-lactamases. The structure of the complex with the transition-state analogue, iodo-acetamido-phenyl boronic acid, shows that the inhibitor is covalently bound to the active-site serine (Ser64). Binding of the inhibitor within the active site is compared with previously determined structures of complexes with other class C enzymes. The structure of the boronic acid adduct indicates ways to improve the affinity of this class of inhibitors. This structure of 908R class C beta-lactamase in complex with a transition-state analogue provides further insights into the mechanism of action of these hydrolases.
Wouters
J
J
Institut de Recherche Microbiologiques JM Wiame, Brussels, Belgium. jwouters@dbm.ulb.ac.be
Fonzé
E
E
Vermeire
M
M
Frère
J-M
JM
Charlier
P
P
D001051:Apoenzymes / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry; D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D016972:Enterobacter cloacae / Q000201:enzymology*; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D001618:beta-Lactamases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism
D001051:Apoenzymes; D001897:Boronic Acids; D008024:Ligands; D001618:beta-Lactamases