2QPN

GES-1 beta-lactamase

Summary for 2QPN

• Entry DOI: 10.2210/pdb2qpn/pdb
• Descriptor: Beta-lactamase GES-1, SULFATE ION (3 entities in total)
• Functional Keywords: beta-lactamase, apo-enzyme, plasmid, hydrolase
• Biological source: Klebsiella pneumoniae
• Total number of polymer chains: 2
• Total formula weight: 62577.00

Authors

Smith, C.A.,Caccamo, M.,Kantardjieff, K.A.,Vakulenko, S. (deposition date: 2007-07-24, release date: 2008-08-12, Last modification date: 2024-10-30)

Primary citation

Smith, C.A.,Caccamo, M.,Kantardjieff, K.A.,Vakulenko, S.
Structure of GES-1 at atomic resolution: insights into the evolution of carbapenamase activity in the class A extended-spectrum beta-lactamases.
Acta Crystallogr.,Sect.D, 63:982-992, 2007

PubMed Abstract: The structure of the class A extended-spectrum beta-lactamase GES-1 from Klebsiella pneumoniae has been determined to 1.1 A resolution. GES-1 has the characteristic active-site disulfide bond of the carbapenemase family of beta-lactamases and has a structure that is very similar to those of other known carbapenemases, including NMC-A, SME-1 and KPC-2. Most residues implicated in the catalytic mechanism of this class of enzyme are present in the GES-1 active site, including Ser70, which forms a covalent bond with the carbonyl C atom of the beta-lactam ring of the substrate during the formation of an acyl-enzyme intermediate, Glu166, which is implicated as both the acylation and deacylation base, and Lys73, which is also implicated as the acylation base. A water molecule crucial to catalysis is observed in an identical location as in other class A beta-lactamases, interacting with the side chains of Ser70 and Glu166. One important residue, Asn170, also normally a ligand for the hydrolytic water, is missing from the GES-1 active site. This residue is a glycine in GES-1 and the enzyme is unable to hydrolyze imipenem. This points to this residue as being critically important in the hydrolysis of this class of beta-lactam substrate. This is further supported by flexible-docking studies of imipenem with in silico-generated Gly170Asn and Gly170Ser mutant GES-1 enzymes designed to mimic the active sites of imipenem-hydrolyzing point mutants GES-2 and GES-5.

PubMed: 17704567
DOI: 10.1107/S0907444907036955

Experimental method

X-RAY DIFFRACTION (1.1 Å)