Kavli Affiliate: Michael Beer
| Authors: Hira Jabeen, Michael Beer, James Spencer, Marc W van der Kamp, H Adrian Bunzel and Adrian J Mulholland
| Summary:
MAntimicrobial resistance is a public health crisis. Limited understanding of the catalytic drivers in resistance-mediating enzymes such as β-lactamases hinders our ability to combat this crisis. Here, we dissect the catalytic contributions of active-site electric fields in class A β-lactamases. We studied the enzymatic hydrolysis of a carbapenem antibiotic by QM/MM molecular dynamics simulations and quantified active-site fields with a custom-made script. We discovered that the fields correlate well with activity and identified seven positions, some distal, that distinguish efficient carbapenemases. Electric-field analysis may help predict the activity of β-lactamases and guide antibiotic and enzyme design. Electric field script: https://www.github.com/bunzela/FieldTools