Electric fields determine carbapenemase activity in class A β-lactamases
ABSTRACT Antimicrobial 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 Figure <jats:fig id="ufig1" position="float" fig-type="figure" orientation="portrait"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="565607v1_ufig1" position="float" orientation="portrait" /></jats:fig>Electric field script:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.github.com/bunzela/FieldTools">www.github.com/bunzela/FieldTools</jats:ext-link>.
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 09. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jabeen, Hira [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| doi: |
10.1101/2023.11.04.565607 |
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| PPN (Katalog-ID): |
XBI041435532 |
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| 245 | 1 | 0 | |a Electric fields determine carbapenemase activity in class A β-lactamases |
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| 520 | |a ABSTRACT Antimicrobial 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 Figure <jats:fig id="ufig1" position="float" fig-type="figure" orientation="portrait"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="565607v1_ufig1" position="float" orientation="portrait" /></jats:fig>Electric field script:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.github.com/bunzela/FieldTools">www.github.com/bunzela/FieldTools</jats:ext-link> | ||
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| 700 | 1 | |a Beer, Michael |0 (orcid)0000-0002-3879-3339 |4 aut | |
| 700 | 1 | |a Spencer, James |0 (orcid)0000-0002-4602-0571 |4 aut | |
| 700 | 1 | |a van der Kamp, Marc W. |0 (orcid)0000-0002-8060-3359 |4 aut | |
| 700 | 1 | |a Bunzel, H. Adrian |0 (orcid)0000-0001-6427-368X |4 aut | |
| 700 | 1 | |a Mulholland, Adrian J. |0 (orcid)0000-0003-1015-4567 |4 aut | |
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