Accès ouvert
2026
preprint
OpenAlex
Abbie Lear, Elliot W. Chan, Kirill Zinovjev, Marc W. van der Kamp et autres
Kemp elimination has become a benchmark for de novo enzyme design due to its simplicity and detailed mechanistic understanding but accurate barrier calculations are required to understand the difference in activity between designed Kemp eliminases. QM/MM MD simulations are capable of calculating …
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2026
preprint
OpenAlex
Elliot W. Chan, Michael Beer, Kirill Zinovjev, James Spencer et autres
Bacterial resistance to carbapenems (potent β-lactam antibiotics) is a critical global health threat. The primary cause is β-lactamase enzymes that hydrolyze antibiotics. Previously, carbapenems resisted breakdown, making them ‘last resort’ antibiotics, but enzymes with carbapenemase activity have become widespread. Understanding and predicting …
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2026
article
OpenAlex
Daojiong Wang, Adrian J. Mulholland, James Spencer, Marc W. van der Kamp
High Resolution Image Download MS PowerPoint Slide The β-lactamase OXA-48 efficiently hydrolyzes carbapenem antibiotics, especially imipenem. Carbapenem resistance is a rising clinical concern and is frequently associated with OXA-48 and its variants. OXA-48 variants carrying different mutations in the β 5 –β …
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2026
preprint
OpenAlex
Joseph F. Hoff, Michael Beer, Philip Hinchliffe, Catherine L. Tooke et autres
Abstract OXA-48 is a globally disseminated class D serine β-lactamase that efficiently confers resistance to a range of β-lactam antibiotics, including carbapenems, the most potent such agents versus Enterobacterales ( Escherichia coli and relatives). Here we characterise the interactions of OXA-48 with …
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Accès ouvert
2025
article
OpenAlex
Diana‐Florentina Veselu, Deborah K. Shoemark, Marc W. van der Kamp
Cystic Fibrosis (CF), one of the most common life-shortening autosomal recessive diseases, arises from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and leads to severe respiratory and digestive dysfunction. CFTR-targeting therapies such as ivacaftor have transformed CF care by …
gb
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2025
article
OpenAlex
Reynier Suardíaz, Shakir Ali Siddiqui, Hanna Kwon, Marc W. van der Kamp et autres
Local electric fields guide protons toward the heme through two distinct electrostatic funnels at the γ- and δ-edges in heme peroxidases. Water-mediated pathways enable proton exchange with key residues such as Arg38 and His42. These findings reveal that nature pre-organizes electrostatic funnels …
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Accès ouvert
2025
article
OpenAlex
Reynier Suardíaz, Shakir Ali Siddiqui, Hanna Kwon, Marc W. van der Kamp et autres
Local electric fields guide protons toward the heme through two distinct electrostatic funnels at the γ- and δ-edges in heme peroxidases. Water-mediated pathways enable proton exchange with key residues such as Arg38 and His42. These findings reveal that nature pre-organizes electrostatic funnels …
es, gb
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Accès ouvert
2025
article
OpenAlex
Reynier Suardíaz, Shakir Ali Siddiqui, Hanna Kwon, Marc W. van der Kamp et autres
Abstract The active sites of heme enzymes have evolved to control the formation of highly reactive intermediates in oxidative catalysis. Proton delivery to the heme is essential, yet the mechanisms of proton delivery remain poorly understood. Here, we identify routes and drivers …
es, gb
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Accès ouvert
2025
article
OpenAlex
Reynier Suardíaz, Shakir Ali Siddiqui, Hanna Kwon, Marc W. van der Kamp et autres
The active sites of heme enzymes have evolved to control the formation of highly reactive intermediates in oxidative catalysis. Proton delivery to the heme is essential, yet the mechanisms of proton delivery remain poorly understood. Here, we identify routes and drivers of …
es, gb
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Accès ouvert
2025
article
OpenAlex
Michael Beer, Philip Hinchliffe, Marko Hanževački, Christopher R. Bethel et autres
β-Lactamase-catalysed hydrolysis is the primary form of β-lactam antibiotic resistance in Gram-negative bacteria. The penicillanic acid sulfone (PAS) enmetazobactam is thought to inhibit extended-spectrum β-lactamases (ESBLs) by fragmentation of an initial acyl-enzyme to form an active-site lysinoalanine cross link. We investigate interactions …
gb, us, ch
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Accès ouvert
2025
article
OpenAlex
Emily Lythell, Jack Badley, Reynier Suardíaz, Catherine L. Tooke et autres
High Resolution Image Download MS PowerPoint Slide The Mobile Colistin Resistance (MCR) phosphoethanolamine (PEtN) transferase is a plasmid-borne enzyme responsible for colistin antibiotic resistance in Escherichia coli, the most important antimicrobial-resistant bacterial pathogen worldwide. Bacterial PEtN transferases like MCR comprise periplasmic catalytic …
gb, es, pt
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Accès ouvert
2025
preprint
OpenAlex
Diana‐Florentina Veselu, Deborah K. Shoemark, Marc W. van der Kamp
Abstract Cystic fibrosis (CF), one of the most common life-shortening autosomal recessive diseases, arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and leads to severe respiratory and digestive dysfunction. CFTR-targeting therapies such as ivacaftor have transformed CF care …
gb
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