ArticleeLife2020
Comprehensive exploration of the translocation, stability and substrate recognition requirements in VIM-2 lactamase.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Molecular Characterization and In Silico Functional Insights into Carbapenem Resistance in ClinicalPathogens (Basel, Switzerland) · 2026Article
- Multidomain DNA-Protein Mining Reveals Polymorphic Variations in RhlB Enhancing Monorhamnolipid Biosynthesis.ACS synthetic biology · 2026Article
- DEX: a consensus-based amino acid exchangeability measure for improved codon substitution modelling.bioRxiv : the preprint server for biology · 2026Article
- Decoding the substrate specificity landscape of a promiscuous enzyme through multi-substrate mutational scanning.Nature communications · 2026Article
- Genetic diversity, biochemical properties, epidemiology, and detection methods of IMP- and VIM-type carbapenemases.Clinical microbiology reviews · 2025Review
- Reviving Furosemide as a Metallo-β-Lactamase Inhibitor against MDRJournal of microbiology and biotechnology · 2025Article
- Neutral drift upon threshold-like selection promotes variation in antibiotic resistance phenotype.Nature communications · 2024Article
- Sequence modeling and design from molecular to genome scale with Evo.Science (New York, N.Y.) · 2024Article
- Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning.Nature communications · 2024Article
- Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage.Genome biology · 2024Article
- Article
- Rapid evolutionary change in trait correlations of single proteins.Nature communications · 2024Article
- High temperature delays and low temperature accelerates evolution of a new protein phenotype.Nature communications · 2024Article
- Measuring differential fitness costs and interactions between genetic cassettes using fluorescent spectrophotometry.Applied and environmental microbiology · 2024Article
- Redirecting pantoprazole as a metallo-beta-lactamase inhibitor in carbapenem-resistantFrontiers in pharmacology · 2024Article
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- Protein engineering via sequence-performance mapping.Cell systems · 2023Review
- Loop dynamics and the evolution of enzyme activity.Nature reviews. Chemistry · 2023Review
- In vitro activity of celastrol in combination with thymol against carbapenem-resistant Klebsiella pneumoniae isolates.The Journal of antibiotics · 2022Article
- Asymmetrical dose responses shape the evolutionary trade-off between antifungal resistance and nutrient use.Nature ecology & evolution · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Metallo-β-lactamases (MBLs) degrade a broad spectrum of β-lactam antibiotics, and are a major disseminating source for multidrug resistant bacteria. Despite many biochemical studies in diverse MBLs, molecular understanding of the roles of residues in the enzyme's stability and function, and especially substrate specificity, is lacking. Here, we employ deep mutational scanning (DMS) to generate comprehensive single amino acid variant data on a major clinical MBL, VIM-2, by measuring the effect of thousands of VIM-2 mutants on the degradation of three representative classes of β-lactams (ampicillin, cefotaxime, and meropenem) and at two different temperatures (25°C and 37°C). We revealed residues responsible for expression and translocation, and mutations that increase resistance and/or alter substrate specificity. The distribution of specificity-altering mutations unveiled distinct molecular recognition of the three substrates. Moreover, these function-altering mutations are frequently observed among naturally occurring variants, suggesting that the enzymes have continuously evolved to become more potent resistance genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.