ArticleThe Journal of biological chemistry2013
Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121: insights from biochemical studies and crystal structures.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 53 citations in OpenAlex.
- Azole chroman-4-one, tetralone and chromen-4-one derivatives: synthesis, Mycobacterium tuberculosis CYP121A1 enzyme inhibition and antimycobacterial activity.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- 3-(Pyridine-3-ylmethylene)chroman-4-one and tetralone derivatives: synthesis,RSC medicinal chemistry · 2026Article
- Structure-Function Analysis of the EssentialInternational journal of molecular sciences · 2024Article
- Natural and engineered cyclodipeptides: Biosynthesis, chemical diversity, and engineering strategies for diversification and high-yield bioproduction.Engineering microbiology · 2023Review
- Synthesis, biological evaluation and computational studies of pyrazole derivatives asRSC medicinal chemistry · 2022Article
- Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents.Current research in pharmacology and drug discovery · 2022Review
- Structure-Activity Relationship and Mode-Of-Action Studies Highlight 1-(4-Biphenylylmethyl)-1H-imidazole-Derived Small Molecules as Potent CYP121 Inhibitors.ChemMedChem · 2021Article
- Multiple drug binding modes in Mycobacterium tuberculosis CYP51B1.Journal of inorganic biochemistry · 2020Article
- Clobetasol Propionate Is a Heme-Mediated Selective Inhibitor of Human Cytochrome P450 3A5.Journal of medicinal chemistry · 2020Article
- Substrate-Assisted Hydroxylation andACS catalysis · 2020Article
- Evaluation of Luminogenic Substrates as Probe Substrates for Bacterial Cytochrome P450 Enzymes: Application toSLAS discovery : advancing life sciences R & D · 2019Article
- Comparative genomics of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members emphasizing tRNA and non-coding RNA.BMC evolutionary biology · 2019Article
- Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?Applied microbiology and biotechnology · 2019Review
- A Promiscuous Cytochrome P450 Hydroxylates Aliphatic and Aromatic C-H Bonds of Aromatic 2,5-Diketopiperazines.Chembiochem : a European journal of chemical biology · 2019Article
- Comparison of Antifungal Azole Interactions with Adult Cytochrome P450 3A4 versus Neonatal Cytochrome P450 3A7.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Biosynthesis of Heptacyclic Duclauxins Requires Extensive Redox Modifications of the Phenalenone Aromatic Polyketide.Journal of the American Chemical Society · 2018Article
- Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system.Journal of inorganic biochemistry · 2018Review
- Probing Ligand Exchange in the P450 Enzyme CYP121 from Mycobacterium tuberculosis: Dynamic Equilibrium of the Distal Heme Ligand as a Function of pH and Temperature.Journal of the American Chemical Society · 2017Article
- Cross-linking of dicyclotyrosine by the cytochrome P450 enzyme CYP121 fromThe Journal of biological chemistry · 2017Article
- The Search for Herbal Antibiotics: An In-Silico Investigation of Antibacterial Phytochemicals.Antibiotics (Basel, Switzerland) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 CYP121 is essential for the viability of Mycobacterium tuberculosis. Studies in vitro show that it can use the cyclodipeptide cyclo(l-Tyr-l-Tyr) (cYY) as a substrate. We report an investigation of the substrate and reaction specificities of CYP121 involving analysis of the interaction between CYP121 and 14 cYY analogues with various modifications of the side chains or the diketopiperazine (DKP) ring. Spectral titration experiments show that CYP121 significantly bound only cyclodipeptides with a conserved DKP ring carrying two aryl side chains in l-configuration. CYP121 did not efficiently or selectively transform any of the cYY analogues tested, indicating a high specificity for cYY. The molecular determinants of this specificity were inferred from both crystal structures of CYP121-analog complexes solved at high resolution and solution NMR spectroscopy of the analogues. Bound cYY or its analogues all displayed a similar set of contacts with CYP121 residues Asn(85), Phe(168), and Trp(182). The propensity of the cYY tyrosyl to point toward Arg(386) was dependent on the presence of the DKP ring that limits the conformational freedom of the ligand. The correct positioning of the hydroxyl of this tyrosyl was essential for conversion of cYY. Thus, the specificity of CYP121 results from both a restricted binding specificity and a fine-tuned P450 substrate relationship. These results document the catalytic mechanism of CYP121 and improve our understanding of its function in vivo. This work contributes to progress toward the design of inhibitors of this essential protein of M. tuberculosis that could be used for antituberculosis therapy.
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.