ArticleBiochemistry2016
Structural Insights into Mycobacterium tuberculosis Rv2671 Protein as a Dihydrofolate Reductase Functional Analogue Contributing to para-Aminosalicylic Acid Resistance.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Design, synthesis and antitubercular evaluation of novel 5,6-diphenyl-1,2,4-triazine-piperazine derivatives targeting mycobacterial dihydrofolate reductase.ADMET & DMPK · 2026Article
- Flavin and deazaflavin biosynthesis in mycobacteria: relevance to physiology, implications for drug discovery, MR-1 antigenicity, and vaccine development.Frontiers in immunology · 2025Review
- Novel Prodrug Strategies for the Treatment of Tuberculosis.Chemistry, an Asian journal · 2024Review
- The T120P or M172V mutation onEmerging microbes & infections · 2024Article
- The aminosalicylate - folate connection.Drug metabolism reviews · 2024Review
- Polypharmacology-Driven Discovery and Design of Highly Selective, Dual and Multitargeting Inhibitors ofCurrent drug targets · 2024Review
- Competition between HAntibiotics (Basel, Switzerland) · 2023Article
- Whole genome sequencing reveals candidate genes involving in PAS resistance in M. Tuberculosis isolated from patients in Thailand.World journal of microbiology & biotechnology · 2023Article
- Dual-TargetInternational journal of molecular sciences · 2023Article
- Aryl-n-hexanamide linked enaminones of usnic acid as promising antimicrobial agents.Molecular diversity · 2023Article
- NADP(H)-dependent biocatalysis without adding NADP(H).Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Molecular basis for avirulence of spontaneous variants of Porphyromonas gingivalis: Genomic analysis of strains W50, BE1 and BR1.Molecular oral microbiology · 2022Article
- Modulatory Impact of the sRNA Mcr11 in Two Clinical Isolates of Mycobacterium tuberculosis.Current microbiology · 2022Article
- Genome-Wide Essentiality Analysis ofmBio · 2021Article
- Multitargeting Compounds: A Promising Strategy to Overcome Multi-Drug Resistant Tuberculosis.Molecules (Basel, Switzerland) · 2020Review
- Drugging the Folate Pathway in Mycobacterium tuberculosis: The Role of Multi-targeting Agents.Cell chemical biology · 2019Article
- Identification of potent chromone embedded [1,2,3]-triazoles as novel anti-tubercular agents.Royal Society open science · 2018Article
- Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae.Nature communications · 2018Article
- Deletion ofAntimicrobial agents and chemotherapy · 2017Article
- dfrA thyA Double Deletion in para-Aminosalicylic Acid-Resistant Mycobacterium tuberculosis Beijing Strains.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) Rv2671 is annotated as a 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione 5'-phosphate (AROPP) reductase (RibD) in the riboflavin biosynthetic pathway. Recently, a strain of Mtb with a mutation in the 5' untranslated region of Rv2671, which resulted in its overexpression, was found to be resistant to dihydrofolate reductase (DHFR) inhibitors including the anti-Mtb drug para-aminosalicylic acid (PAS). In this study, a biochemical analysis of Rv2671 showed that it was able to catalyze the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), which explained why the overexpression of Rv2671 was sufficient to confer PAS resistance. We solved the structure of Rv2671 in complex with the NADP(+) and tetrahydrofolate (THF), which revealed the structural basis for the DHFR activity. The structures of Rv2671 complexed with two DHFR inhibitors, trimethoprim and trimetrexate, provided additional details of the substrate binding pocket and elucidated the differences between their inhibitory activities. Finally, Rv2671 was unable to catalyze the reduction of AROPP, which indicated that Rv2671 and its closely related orthologues are not involved in riboflavin biosynthesis.
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