ArticlePloS one2012
A catalytic mechanism for cysteine N-terminal nucleophile hydrolases, as revealed by free energy simulations.
Article in PloS one, 2012. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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, 76 citations in OpenAlex.
- Challenges and opportunities in the enzymatic recycling of nylons.Nature chemical biology · 2026Review
- Structural and oligomeric characterization of substrate- and product-selective nylon hydrolases.bioRxiv : the preprint server for biology · 2026Article
- The Crystal Structure of Human Transport and Golgi Organization 2 Homolog (TANGO2) Protein Reveals an αββα-Fold Arrangement.Proteins · 2026Article
- Enzymatic Synthesis of β-lactam Antibiotics: From Enzyme Dataset Construction to Action Mechanism and Semi-Rational Design.Current protein & peptide science · 2026Review
- On Free Energy Calculations in Drug Discovery.Accounts of chemical research · 2025Article
- 1,2,4-Thiadiazolidin-3,5-Diones as Inhibitors of Cysteine Proteases.Molecules (Basel, Switzerland) · 2025Article
- Nanomaterial scaffolds for enzymatic polymer degradation: a tool to advance current biodegradation assessments of polymers in liquid formulation.Bioscience nanotechnology · 2025Review
- First Insight into the Degradome ofInternational journal of molecular sciences · 2024Article
- Article
- Elucidation of the Active Form and Reaction Mechanism in Human Asparaginase Type III Using Multiscale Simulations.Journal of chemical information and modeling · 2023Article
- Role of Stereochemistry on the Biological Activity of Nature-Inspired 3-Br-Acivicin Isomers and Derivatives.Molecules (Basel, Switzerland) · 2023Article
- Mechanistic Modeling of Lys745 Sulfonylation in EGFR C797S Reveals Chemical Determinants for Inhibitor Activity and Discriminates Reversible from Irreversible Agents.Journal of chemical information and modeling · 2023Article
- Review
- Free-Energy Simulations Support a Lipophilic Binding Route for Melatonin Receptors.Journal of chemical information and modeling · 2022Article
- Functional and Phylogenetic Diversity of BSH and PVA Enzymes.Microorganisms · 2021Review
- Density-functional tight-binding: basic concepts and applications to molecules and clusters.Advances in physics: X · 2020Article
- The complex structure of bile salt hydrolase from Lactobacillus salivarius reveals the structural basis of substrate specificity.Scientific reports · 2019Article
- Covalent Inhibitors ofACS medicinal chemistry letters · 2019Article
- Bile salt hydrolases: Gatekeepers of bile acid metabolism and host-microbiome crosstalk in the gastrointestinal tract.PLoS pathogens · 2019Article
- Bile salt hydrolases: Structure and function, substrate preference, and inhibitor development.Protein science : a publication of the Protein Society · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The N-terminal nucleophile (Ntn) hydrolases are a superfamily of enzymes specialized in the hydrolytic cleavage of amide bonds. Even though several members of this family are emerging as innovative drug targets for cancer, inflammation, and pain, the processes through which they catalyze amide hydrolysis remains poorly understood. In particular, the catalytic reactions of cysteine Ntn-hydrolases have never been investigated from a mechanistic point of view. In the present study, we used free energy simulations in the quantum mechanics/molecular mechanics framework to determine the reaction mechanism of amide hydrolysis catalyzed by the prototypical cysteine Ntn-hydrolase, conjugated bile acid hydrolase (CBAH). The computational analyses, which were confirmed in water and using different CBAH mutants, revealed the existence of a chair-like transition state, which might be one of the specific features of the catalytic cycle of Ntn-hydrolases. Our results offer new insights on Ntn-mediated hydrolysis and suggest possible strategies for the creation of therapeutically useful inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.