Electric fields determine carbapenemase activity in class A β-lactamases

Author:

Jabeen HiraORCID,Beer MichaelORCID,Spencer JamesORCID,van der Kamp Marc W.ORCID,Bunzel H. AdrianORCID,Mulholland Adrian J.ORCID

Abstract

ABSTRACTAntimicrobial 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.Abstract FigureElectric field script:www.github.com/bunzela/FieldTools

Publisher

Cold Spring Harbor Laboratory

Reference60 articles.

1. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis;The Lancet,2022

2. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report: Early Implementation 2020. World Health Organization (2020).

3. Antibiotic Resistance Threats in the United States. Centers for Disease Control and Prevention (2019).

4. Tackling antimicrobial resistance 2019–2024: The UK’s five-year national action plan. HM Gov. (2019).

5. Turning plans into action for antimicrobial resistance (AMR) Working Paper 2.0: Implementation and coordination. World Health Organization (2019).

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3