ArticlePloS one2014
Biochemical characterization of quinolinic acid phosphoribosyltransferase from Mycobacterium tuberculosis H37Rv and inhibition of its activity by pyrazinamide.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Pyrazinoic acid, the active form of the anti-tuberculosis drug pyrazinamide, and aromatic carboxylic acid analogs are protonophores.Frontiers in molecular biosciences · 2024Article
- Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis.Frontiers in immunology · 2023Review
- Article
- The Prospective Synergy of Antitubercular Drugs With NAD Biosynthesis Inhibitors.Frontiers in microbiology · 2020Review
- Pharmacological and Molecular Mechanisms Behind the Sterilizing Activity of Pyrazinamide.Trends in pharmacological sciences · 2019Review
- Derivatives of 3-Aminopyrazine-2-carboxamides: Synthesis, Antimicrobial Evaluation, and in Vitro Cytotoxicity.Molecules (Basel, Switzerland) · 2019Article
- Design, Synthesis and Evaluation ofMolecules (Basel, Switzerland) · 2018Article
- Design, synthesis and antimycobacterial activity of hybrid molecules combining pyrazinamide with a 4-phenylthiazol-2-amine scaffold.MedChemComm · 2018Article
- Hit Generation in TB Drug Discovery: From Genome to Granuloma.Chemical reviews · 2018Review
- Pyrazinoic Acid Inhibits Mycobacterial Coenzyme A Biosynthesis by Binding to Aspartate Decarboxylase PanD.ACS infectious diseases · 2017Article
- The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: SnapshotMolecules (Basel, Switzerland) · 2017Article
- Ureidopyrazine Derivatives: Synthesis and Biological Evaluation as Anti-Infectives and Abiotic Elicitors.Molecules (Basel, Switzerland) · 2017Article
- Pyrazinamide Is Active against Mycobacterium tuberculosis Cultures at Neutral pH and Low Temperature.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quinolinic acid phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) is a key enzyme in the de novo pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis and a target for the development of new anti-tuberculosis drugs. QAPRTase catalyzes the synthesis of nicotinic acid mononucleotide from quinolinic acid (QA) and 5-phosphoribosyl-1-pyrophosphate (PRPP) through a phosphoribosyl transfer reaction followed by decarboxylation. The crystal structure of QAPRTase from Mycobacterium tuberculosis H37Rv (MtQAPRTase) has been determined; however, a detailed functional analysis of MtQAPRTase has not been published. Here, we analyzed the enzymatic activities of MtQAPRTase and determined the effect on catalysis of the anti-tuberculosis drug pyrazinamide (PZA). The optimum temperature and pH for MtQAPRTase activity were 60°C and pH 9.2. MtQAPRTase required bivalent metal ions and its activity was highest in the presence of Mg2+. Kinetic analyses revealed that the Km values for QA and PRPP were 0.08 and 0.39 mM, respectively, and the kcat values for QA and PRPP were 0.12 and 0.14 [s-1], respectively. When the amino acid residues of MtQAPRTase, which may interact with QA, were substituted with alanine residues, catalytic activity was undetectable. Further, PZA, which is an anti-tuberculosis drug and a structural analog of QA, markedly inhibited the catalytic activity of MtQAPRTase. The structure of PZA may provide the basis for the design of new inhibitors of MtQAPRTase. These findings provide new insights into the catalytic properties of MtQAPRTase.
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