3HRE

X-ray crystallographic structure of CTX-M-9 S70G

Summary for 3HRE

• Entry DOI: 10.2210/pdb3hre/pdb
• Related: 3HLW
• Descriptor: CTX-M-9 extended-spectrum beta-lactamase, PHOSPHATE ION (3 entities in total)
• Functional Keywords: beta-lactamase, blse, ctx-m-9, antibiotic resistance, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 56169.85

Authors

Delmas, J.,Leyssene, D.,Dubois, D.,Vazeille, E.,Robin, F.,Bonnet, R. (deposition date: 2009-06-09, release date: 2010-06-16, Last modification date: 2023-11-01)

Primary citation

Delmas, J.,Leyssene, D.,Dubois, D.,Birck, C.,Vazeille, E.,Robin, F.,Bonnet, R.
Structural insights into substrate recognition and product expulsion in CTX-M enzymes.
J.Mol.Biol., 400:108-120, 2010

PubMed Abstract: beta-Lactamase-mediated resistance to beta-lactam antibiotics poses a major threat to our antibiotic armamentarium. Among beta-lactamases, a significant threat comes from enzymes that hydrolyze extended-spectrum cephalosporins such as cefotaxime. Among the enzymes that exhibit this phenotype, the CTX-M family is found worldwide. These enzymes have a small active site, which makes it difficult to explain how they hydrolyze the bulky extended-spectrum cephalosporins into the binding site. We investigated noncovalent substrate recognition and product release in CTX-M enzymes using steered molecular dynamics simulation and X-ray diffraction. An arginine residue located far from the binding site favors the capture and tracking of substrates during entrance into the catalytic pocket. We show that the accommodation of extended-spectrum cephalosporins by CTX-M enzymes induced subtle changes in the active site and established a high density of electrostatic interactions. Interestingly, the product of the catalytic reaction initiates its own release because of steric hindrances and electrostatic repulsions. This suggests that there exists a general mechanism for product release for all members of the beta-lactamase family and probably for most carboxypeptidases.

PubMed: 20452359
DOI: 10.1016/j.jmb.2010.04.062

Experimental method

X-RAY DIFFRACTION (1.45 Å)