A low-barrier proton shared between two aspartates acts as a conformational switch that changes the substrate specificity of the β-lactamase BlaC.

Abstract excerpt

Serine β-lactamases inactivate β-lactam antibiotics in a two-step mechanism comprising acylation and deacylation. For the deacylation step, a water molecule is activated by a conserved glutamate residue to release the adduct from the enzyme. The third-generation cephalosporin ceftazidime is a poor substrate for the class A β-lactamase BlaC from Mycobacterium tuberculosis but it can be hydrolyzed faster when the...

Topics

• Substrate Specificity
• beta-Lactamases
• Hydrogen-Ion Concentration
• Aspartic Acid
• Protons
• Protein Conformation
• Catalytic Domain
• Ceftazidime
• Kinetics
• Models, Molecular
• Mycobacterium tuberculosis
• Mutation