X-ray structure of the ZnII beta-lactamase from Bacteroides fragilis in an orthorhombic crystal form.
beta-Lactamases are extracellular or periplasmic bacterial enzymes which confer resistance to beta-lactam antibiotics. On the basis of their catalytic mechanisms, they can be divided into two major groups: active-site serine enzymes (classes A, C and D) and the ZnII enzymes (class B). The first crystal structure of a class B enzyme, the metallo-beta-lactamase from Bacillus cereus, has been solved at 2.5 A resolution [Carfi, Pares, Duée, Galleni, Duez, Frère & Dideberg (1995). EMBO J. 14, 4914-4921]. Recently, the crystal structure of the metallo-beta-lactamase from Bacteroides fragilis has been determined in a tetragonal space group [Concha, Rasmussen, Bush & Herzberg (1996). Structure, 4, 823-836]. The structure of the metallo-beta-lactamase from B. fragilis in an orthorhombic crystal form at 2.0 A resolution is reported here. The final crystallographic R is 0.196 for all the 32501 observed reflections in the range 10-2.0 A. The refined model includes 458 residues, 437 water molecules, four zinc and two sodium ions. These structures are discussed with reference to Zn binding and activity. A catalytic mechanism is proposed which is coherent with metallo-beta-lactamases being active with either one Zn ion (as in Aeromonas hydrophila) or two Zn ions (as in B. fragilis) bound to the protein.
LCM, Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS), Grenoble, France.
A
A
Carfi
E
E
Duée
R
R
Paul-Soto
M
M
Galleni
J M
JM
Frère
O
O
Dideberg
D000595:Amino Acid Sequence; D001441:Bacteroides fragilis / Q000201:enzymology*; D020134:Catalytic Domain; D003461:Crystallography; D018360:Crystallography, X-Ray; D008666:Metalloendopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015203:Reproducibility of Results; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000737:chemistry*; D001618:beta-Lactamases / Q000737:chemistry*
D008666:Metalloendopeptidases; D001618:beta-Lactamases; D015032:Zinc