ArticleThe Journal of biological chemistry2011
Inactivation kinetics of a new target of beta-lactam antibiotics.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Peptide Mimetic Platform for Activity Profiling of Mycobacterial l,d-Transpeptidases.Biochemistry · 2026Article
- Activity Profiling of Mycobacterial L,D-Transpeptidases.bioRxiv : the preprint server for biology · 2026Article
- Peptidoglycan LD-Transpeptidases.Antibiotics (Basel, Switzerland) · 2025Review
- Targeting mycobacterial transpeptidases: evaluating the roles of Ldt and PBP inhibition in suppressingAntimicrobial agents and chemotherapy · 2025Article
- Biochemical and crystallographic studies of L,D-transpeptidase 2 from Mycobacterium tuberculosis with its natural monomer substrate.Communications biology · 2024Article
- A distinctive family of L,D-transpeptidases catalyzing L-Ala-mDAP crosslinks in Alpha- and Betaproteobacteria.Nature communications · 2024Article
- High-throughput screen with the l,d-transpeptidase LdtChemical science · 2023Article
- The l,d-Transpeptidase LdtACS infectious diseases · 2022Article
- Competing off-loading mechanisms of meropenem from an l,d-transpeptidase reduce antibiotic effectiveness.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Phylogenetic and Biochemical Analyses of Mycobacterial l,d-Transpeptidases Reveal a Distinct Enzyme Class That Is Preferentially Acylated by Meropenem.ACS infectious diseases · 2019Article
- Select β-Lactam Combinations Exhibit Synergy againstAntimicrobial agents and chemotherapy · 2019Article
- Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-ResistantAntimicrobial agents and chemotherapy · 2019Article
- Copper inhibits peptidoglycan LD-transpeptidases suppressing β-lactam resistance due to bypass of penicillin-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structure and Inhibitor Specificity of L,D-Transpeptidase (LdtMt2) from Mycobacterium tuberculosis and Antibiotic Resistance: Calcium Binding Promotes Dimer Formation.The AAPS journal · 2018Article
- Peptidoglycan Cross-Linking Activity of l,d-Transpeptidases from Clostridium difficile and Inactivation of These Enzymes by β-Lactams.Antimicrobial agents and chemotherapy · 2018Article
- Reversible inactivation of a peptidoglycan transpeptidase by a β-lactam antibiotic mediated by β-lactam-ring recyclization in the enzyme active site.Scientific reports · 2017Article
- LdtFuture microbiology · 2017Article
- Non-classical transpeptidases yield insight into new antibacterials.Nature chemical biology · 2017Article
- β-Lactam Resistance Mechanisms: Gram-Positive Bacteria and Mycobacterium tuberculosis.Cold Spring Harbor perspectives in medicine · 2016Review
- Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.Drug design, development and therapy · 2016Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Peptidoglycan is predominantly cross-linked by serine DD-transpeptidases in most bacterial species. The enzymes are the essential targets of β-lactam antibiotics. However, unrelated cysteine LD-transpeptidases have been recently recognized as a predominant mode of peptidoglycan cross-linking in Mycobacterium tuberculosis and as a bypass mechanism conferring resistance to all β-lactams, except carbapenems such as imipenem, in Enterococcus faecium. Investigation of the mechanism of inhibition of this new β-lactam target showed that acylation of the E. faecium enzyme (Ldt(fm)) by imipenem is irreversible. Using fluorescence kinetics, an original approach was developed to independently determine the catalytic constants for imipenem binding (k(1) = 0.061 μM(-1) min(-1)) and acylation (k(inact) = 4.5 min(-1)). The binding step was limiting at the minimal drug concentration required for bacterial growth inhibition. The Michaelis complex was committed to acylation because its dissociation was negligible. The emergence of imipenem resistance involved substitutions in Ldt(fm) that reduced the rate of formation of the non-covalent complex but only marginally affected the efficiency of the acylation step. The methods described in this study will facilitate development of new carbapenems active on extensively resistant M. tuberculosis.
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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.