ArticleBiochemistry2010
Kinetics and inhibition of nicotinamidase from Mycobacterium tuberculosis.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- TargetingACS omega · 2026Article
- Kinetic Mechanism of the Emergent Anticancer Target, Human ADP-ribosyltransferase 1.Biochemistry · 2025Article
- Phenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activity.PLoS neglected tropical diseases · 2024Article
- Bacterial PncA improves diet-induced NAFLD in mice by enabling the transition from nicotinamide to nicotinic acid.Communications biology · 2023Article
- An insecticide target in mechanoreceptor neurons.Science advances · 2022Article
- Article
- The ratio of nicotinic acid to nicotinamide as a microbial biomarker for assessing cell therapy product sterility.Molecular therapy. Methods & clinical development · 2022Article
- Article
- A Key Enzyme of the NADJournal of bacteriology · 2017Article
- Article
- Meat Intake and the Dose of Vitamin BInternational journal of tryptophan research : IJTR · 2017Review
- Article
- Pyrazinamide Is Active against Mycobacterium tuberculosis Cultures at Neutral pH and Low Temperature.Antimicrobial agents and chemotherapy · 2016Article
- Mechanisms of Pyrazinamide Action and Resistance.Microbiology spectrum · 2013Article
- Big brains, meat, tuberculosis, and the nicotinamide switches: co-evolutionary relationships with modern repercussions?International journal of tryptophan research : IJTR · 2013Article
- The evolutionary portrait of metazoan NAD salvage.PloS one · 2013Article
- Role of metal ions on the activity of Mycobacterium tuberculosis pyrazinamidase.The American journal of tropical medicine and hygiene · 2012Article
- Structural and kinetic isotope effect studies of nicotinamidase (Pnc1) from Saccharomyces cerevisiae.Biochemistry · 2012Article
- Crystal structure of the pyrazinamidase of Mycobacterium tuberculosis: insights into natural and acquired resistance to pyrazinamide.PloS one · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nicotinamidase/pyrazinamidase (PncA) is involved in the NAD+ salvage pathway of Mycobacterium tuberculosis and other bacteria. In addition to hydrolyzing nicotinamide into nicotinic acid, PncA also hydrolyzes the prodrug pyrazinamide to generate the active form of the drug, pyrazinoic acid, which is an essential component of the multidrug treatment of TB. A coupled enzymatic activity assay has been developed for PncA that allows for the spectroscopic observation of enzyme activity. The enzyme activity was essentially pH-independent under the conditions tested; however, the measurement of the pH dependence of iodoacetamide alkylation revealed a pK value of 6.6 for the active site cysteine. Solvent deuterium kinetic isotope effects revealed an inverse value for kcat of 0.64, reconfirming the involvement of a thiol group in the mechanism. A mechanism is proposed for PncA catalysis that is similar to the mechanisms proposed for members of the nitrilase superfamily, in which nucleophilic attack by the active site cysteine generates a tetrahedral intermediate that collapses with the loss of ammonia and subsequent hydrolysis of the thioester bond by water completes the cycle. An inhibitor screen identified the competitive inhibitor 3-pyridine carboxaldehyde with a Ki of 290 nM. Additionally, pyrazinecarbonitrile was found to be an irreversible inactivator of PncA, with a kinact/KI of 975 M(−1) s(−1).
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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.