ArticleBiochemistry2008
Kinetic and chemical mechanism of arylamine N-acetyltransferase from Mycobacterium tuberculosis.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Advances in Key Drug Target Identification and New Drug Development for Tuberculosis.BioMed research international · 2022Review
- Gcn5-RelatedFrontiers in molecular biosciences · 2021Article
- Discovery of a previously unknown biosynthetic capacity of naringenin chalcone synthase by heterologous expression of a tomato gene cluster in yeast.Science advances · 2020Article
- Biochemical Characterization of ArylamineFrontiers in microbiology · 2020Article
- Eis, a novel family of arylalkylamine N-acetyltransferase (EC 2.3.1.87).Scientific reports · 2018Article
- Mycobacterium tuberculosis Arylamine N-Acetyltransferase Acetylates and Thus Inactivates para-Aminosalicylic Acid.Antimicrobial agents and chemotherapy · 2016Article
- New Insights into the Biosynthesis of Fosfazinomycin.Chemical science · 2016Article
- Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery.British journal of pharmacology · 2014Review
- Molecular characterization of a novel N-acetyltransferase from Chryseobacterium sp.Applied and environmental microbiology · 2014Article
- Arylamine N-acetyltransferases: a structural perspective. Comments regarding the BJP paper by Zhou et al., 2013.British journal of pharmacology · 2014Article
- Structural and biochemical characterization of an active arylamine N-acetyltransferase possessing a non-canonical Cys-His-Glu catalytic triad.The Journal of biological chemistry · 2013Article
- Identification of the enzyme responsible for N-acetylation of norfloxacin by Microbacterium sp. Strain 4N2-2.Applied and environmental microbiology · 2013Article
- Interaction of wild type, G68R and L125M isoforms of the arylamine-N-acetyltransferase from Mycobacterium tuberculosis with isoniazid: a computational study on a new possible mechanism of resistance.Journal of molecular modeling · 2012Article
- Kinetics and inhibition of nicotinamidase from Mycobacterium tuberculosis.Biochemistry · 2010Article
- Kinetic mechanism of the Rtt109-Vps75 histone acetyltransferase-chaperone complex.Biochemistry · 2010Article
- Probing the architecture of the Mycobacterium marinum arylamine N-acetyltransferase active site.Protein & cell · 2010Article
- Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars.Protein & cell · 2010Article
- Probing the catalytic potential of the hamster arylamine N-acetyltransferase 2 catalytic triad by site-directed mutagenesis of the proximal conserved residue, Tyr190.The FEBS journal · 2009Article
- Comparison of the Arylamine N-acetyltransferase from Mycobacterium marinum and Mycobacterium tuberculosis.The protein journal · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Arylamine N-acetyltransferases (NATs) are cytosolic enzymes that catalyze the transfer of the acetyl group from acetyl coenzyme A (AcCoA) to the free amino group of arylamines and hydrazines. Previous studies have reported that overexpression of NAT from Mycobacterium smegmatis and Mycobacterium tuberculosis may be responsible for increased resistance to the front-line antitubercular drug, isoniazid, by acetylating and hence inactivating the prodrug. We report the kinetic characterization of M. tuberculosis NAT which reveals that substituted anilines are excellent substrates but that isoniazid is a very poor substrate for this enzyme. We propose that the expression of NAT from M. tuberculosis (TBNAT) is unlikely to be a significant cause of isoniazid resistance. The kinetic parameters for a variety of TBNAT substrates were examined, including 3-amino-4-hydroxybenzoic acid and AcCoA, revealing K m values of 0.32 +/- 0.03 and 0.14 +/- 0.02 mM, respectively. Steady-state kinetic analysis of TBNAT reveals that the enzyme catalyzes the reaction via a bi-bi ping-pong kinetic mechanism. The pH dependence of the kinetic parameters reveals that one enzyme group must be deprotonated for optimal catalytic activity and that two amino acid residues at the active site of the free enzyme are involved in binding and/or catalysis. Solvent kinetic isotope effects suggest that proton transfer steps are not rate-limiting in the overall reaction for substituted aniline substrates but become rate-limiting when poor hydrazide substrates are used.
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.