ArticleBiochemistry2013
Reaction pathway and free energy profile for papain-catalyzed hydrolysis of N-acetyl-Phe-Gly 4-nitroanilide.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Evaluating the protonation state of the catalytic Cys25 in cruzain cysteine protease: A target for Chagas disease.Protein science : a publication of the Protein Society · 2025Article
- Papain-Mediated Conjugation of Peptide Nucleic Acids to Delivery Peptides: A Density Functional Theory/Molecular Mechanics Metadynamics Study in Aqueous and Organic Solvent.The journal of physical chemistry. B · 2024Article
- Unraveling the catalytic mechanism of SARS-CoV-2 papain-like protease with allosteric modulation of C270 mutation using multiscale computational approaches.Chemical science · 2023Article
- Computational Study of the Inhibition of RgpB Gingipain, a Promising Target for the Treatment of Alzheimer's Disease.Journal of chemical information and modeling · 2023Article
- A New Pharmacological Vitreolysis through the Supplement of Mixed Fruit Enzymes for Patients with Ocular Floaters or Vitreous Hemorrhage-Induced Floaters.Journal of clinical medicine · 2022Article
- Between Protein Fold and Nucleophile Identity: Multiscale Modeling of the TEV Protease Enzyme-Substrate Complex.ACS omega · 2022Article
- Mechanisms of Proteolytic Enzymes and Their Inhibition in QM/MM Studies.International journal of molecular sciences · 2021Review
- An insight into the interaction between α-ketoamide- based inhibitor and coronavirus main protease: A detailed in silico study.Biophysical chemistry · 2021Article
- On the Catalytic Activity of the Engineered Coiled-Coil Heptamer Mimicking the Hydrolase Enzymes: Insights from a Computational Study.International journal of molecular sciences · 2020Article
- Revealing the molecular mechanisms of proteolysis of SARS-CoV-2 MChemical science · 2020Article
- Activation and selectivity of OTUB-1 and OTUB-2 deubiquitinylases.The Journal of biological chemistry · 2020Article
- Protease-Catalyzed l-Aspartate Oligomerization: Substrate Selectivity and Computational Modeling.ACS omega · 2020Article
- Artificial cysteine-lipases with high activity and altered catalytic mechanism created by laboratory evolution.Nature communications · 2019Article
- Insights into Ag(i)-catalyzed addition reactions of amino alcohols to electron-deficient olefins: competing mechanisms, role of catalyst, and origin of chemoselectivity.RSC advances · 2018Article
- Efficient promiscuous Knoevenagel condensation catalyzed by papain confined in CuRSC advances · 2018Article
- Article
- Distinct Roles of Catalytic Cysteine and Histidine in the Protease and Ligase Mechanisms of Human Legumain As Revealed by DFT-Based QM/MM Simulations.ACS catalysis · 2017Article
- Catalytic Mechanisms for Cofactor-Free Oxidase-Catalyzed Reactions: Reaction Pathways of Uricase-Catalyzed Oxidation and Hydration of Uric Acid.ACS catalysis · 2017Article
- The Catalytic Mechanism of the Marine-Derived Macrocyclase PatGmac.Chemistry (Weinheim an der Bergstrasse, Germany) · 2016Article
- Activation of Bacteroides fragilis toxin by a novel bacterial protease contributes to anaerobic sepsis in mice.Nature medicine · 2016Article
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5 authors.
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Abstract
Possible reaction pathways for papain-catalyzed hydrolysis of N-acetyl-Phe-Gly 4-nitroanilide (APGNA) have been studied by performing pseudobond first-principles quantum mechanical/molecular mechanical-free energy (QM/MM-FE) calculations. The whole hydrolysis process includes two stages: acylation and deacylation. For the acylation stage of the catalytic reaction, we have explored three possible paths (A, B, and C) and the corresponding free energy profiles along the reaction coordinates. It has been demonstrated that the most favorable reaction path in this stage is path B consisting of two reaction steps: the first step is a proton transfer to form a zwitterionic form (i.e., Cys-S⁻/His-H⁺ ion-pair), and the second step is the nucleophilic attack on the carboxyl carbon of the substrate accompanied by the dissociation of 4-nitroanilide. The deacylation stage includes the nucleophilic attack of a water molecule on the carboxyl carbon of the substrate and dissociation between the carboxyl carbon of the substrate and the sulfhydryl sulfur of Cys25 side chain. The free energy barriers calculated for the acylation and deacylation stages are 20.0 and 10.7 kcal/mol, respectively. Thus, the acylation is rate-limiting. The overall free energy barrier calculated for papain-catalyzed hydrolysis of APGNA is 20.0 kcal/mol, which is reasonably close to the experimentally derived activation free energy of 17.9 kcal/mol.
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