Structure of an extended-spectrum class A beta-lactamase from Proteus vulgaris K1.
The structure of a chromosomal extended-spectrum beta-lactamase (ESBL) having the ability to hydrolyze cephalosporins including cefuroxime and ceftazidime has been determined by X-ray crystallography to 1.75 A resolution. The species-specific class A beta-lactamase from Proteus vulgaris K1 was crystallized at pH 6.25 and its structure solved by molecular replacement. Refinement of the model resulted in crystallographic R and R(free) of 16.9 % and 19.3 %, respectively. The folding of the K1 enzyme is broadly similar to that of non-ESBL TEM-type beta-lactamases (2 A rmsd for C(alpha)) and differs by only 0.35 A for all atoms of six conserved residues in the catalytic site. Other residues promoting extended-spectrum activity in K1 include the side-chains of atypical residues Ser237 and Lys276. These side-chains are linked by two water molecules, one of which lies in the position normally filled by the guanidinium group of Arg244, present in most non-ESBL enzymes but absent from K1. The ammonium group of Lys276, ca 3.5 A from the virtual Arg244 guanidinium position, may interact with polar R2 substitutents on the dihydrothiazene ring of cephalosporins.
Nukaga
Michiyoshi
M
Department of Molecular and Cell Biology, The University of Connecticut, Storrs, CT 06269-3125, USA.
Mayama
Kayoko
K
Crichlow
Gregg V
GV
Knox
James R
JR
D001665:Binding Sites; D018360:Crystallography, X-Ray; D024881:Drug Resistance, Bacterial; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D011514:Proteus vulgaris / Q000145:classification* / Q000201:enzymology*; D001618:beta-Lactamases / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism
D001618:beta-Lactamases