ArticleScientific reports2018
Defining the architecture of KPC-2 Carbapenemase: identifying allosteric networks to fight antibiotics resistance.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Resistance development in KPC-producingMicrobiology spectrum · 2026Article
- Dynamical-nonequilibrium alanine scanning for identifying allosteric positions in proteins.Biophysical journal · 2026Article
- Deep learning insights into β-lactamase dynamics and resistance evolution.The Biochemical journal · 2026Review
- Characterization of KPC-160, a novel Ω-loop-deleted KPC variant on a dual-copy plasmid that confers cefiderocol resistance.Antimicrobial agents and chemotherapy · 2026Article
- Role of Mobilome in Carbapenem Resistance.Antibiotics (Basel, Switzerland) · 2026Review
- Role of Ambler Position 104 in Defining Substrate Specificity in the KPC Family of β-Lactamases.ACS infectious diseases · 2026Article
- Characterization of prophage carrying blaEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Review
- Structural insights into the activity of carbapenemases: understanding the mechanism of action of current inhibitors and informing the design of new carbapenem adjuvants.RSC medicinal chemistry · 2025Review
- Article
- Epidemiology and Genetic Traits of Carbapenemase-Producing Enterobacterales: A Global Threat to Human Health.Antibiotics (Basel, Switzerland) · 2025Review
- Characterization of GQA as a novel β-lactamase inhibitor of CTX-M-15 and KPC-2 enzymes.Microbial cell factories · 2024Article
- Crystal structure of the class A extended-spectrum β-lactamase CTX-M-96 in complex with relebactam at 1.03 Angstrom resolution.Antimicrobial agents and chemotherapy · 2024Article
- Deciphering the Coevolutionary Dynamics of L2 β-Lactamases via Deep Learning.Journal of chemical information and modeling · 2024Article
- Enhancing the activity of β-lactamase inhibitory protein-II with cell-penetrating peptide against KPC-2-carrying Klebsiella pneumoniae.PloS one · 2024Article
- Gating interactions steer loop conformational changes in the active site of the L1 metallo-β-lactamase.eLife · 2023Article
- Article
- Klebsiella pneumoniae Carbapenemase Variants Resistant to Ceftazidime-Avibactam: an Evolutionary Overview.Antimicrobial agents and chemotherapy · 2022Review
- Studies on the Reactions of Biapenem with VIM Metallo β-Lactamases and the Serine β-Lactamase KPC-2.Antibiotics (Basel, Switzerland) · 2022Article
- Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics.eLife · 2021Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
Abstract
The rise of multi-drug resistance in bacterial pathogens is one of the grand challenges facing medical science. A major concern is the speed of development of β-lactamase-mediated resistance in Gram-negative species, thus putting at risk the efficacy of the most recently approved antibiotics and inhibitors, including carbapenems and avibactam, respectively. New strategies to overcome resistance are urgently required, which will ultimately be facilitated by a deeper understanding of the mechanisms that regulate the function of β-lactamases such as the Klebsiella Pneumoniae carbapenemases (KPCs). Using enhanced sampling computational methods together with site-directed mutagenesis, we report the identification of two "hydrophobic networks" in the KPC-2 enzyme, the integrity of which has been found to be essential for protein stability and corresponding resistance. Present throughout the structure, these networks are responsible for the structural integrity and allosteric signaling. Disruption of the networks leads to a loss of the KPC-2 mediated resistance phenotype, resulting in restored susceptibility to different classes of β-lactam antibiotics including carbapenems and cephalosporins. The "hydrophobic networks" were found to be highly conserved among class-A β-lactamases, which implies their suitability for exploitation as a potential target for therapeutic intervention.
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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.