ReviewCurrent topics in medicinal chemistry2012
Adenylating enzymes in Mycobacterium tuberculosis as drug targets.
Review in Current topics in medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- Pharmacological targeting of the mycothiol cysteine ligase MshC in Mycobacteriumabscessus.The Journal of biological chemistry · 2026Article
- Structure, Function, and Inhibition of Adenylosuccinate Lyase (ADSL) fromACS infectious diseases · 2026Article
- Structure and catalytic mechanism of exogenous fatty acid recycling by AasS, a versatile acyl-ACP synthetase.Nature structural & molecular biology · 2025Article
- Design and synthesis of a library of C8-substituted sulfamidoadenosines to probe bacterial permeability.Bioorganic & medicinal chemistry letters · 2024Article
- Computational Insight into Substrate-Induced Conformational Changes in Methionyl-tRNA Synthetase of Mycobacterium Tuberculosis.The protein journal · 2023Article
- A broad inhibitor of acyl-acyl carrier protein synthetases.Biochemistry and biophysics reports · 2023Article
- Polyfluorinated salicylic acid analogs do not interfere with siderophore biosynthesis.Tuberculosis (Edinburgh, Scotland) · 2023Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
- Human Kinase IGF1R/IR Inhibitor Linsitinib Controls the In Vitro and Intracellular Growth ofACS infectious diseases · 2022Article
- Analogues of Pyrimidine Nucleosides as Mycobacteria Growth Inhibitors.Microorganisms · 2022Review
- Solution and Membrane Interaction Dynamics ofBiochemistry · 2021Article
- Article
- Structure of a reaction intermediate mimic in t6A biosynthesis bound in the active site of the TsaBD heterodimer from Escherichia coli.Nucleic acids research · 2021Article
- Structure-based virtual screening of essential Mycobacterium tuberculosis enzymes AspS and KatG for potential inhibitors.Bioinformation · 2021Article
- Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis.European journal of medicinal chemistry · 2020Article
- Dynamic Characterization of Protein and Posttranslational Modification Levels in Mycobacterial Cholesterol Catabolism.mSystems · 2020Article
- Gram-scale preparation of the antibiotic lead compound salicyl-AMS, a potent inhibitor of bacterial salicylate adenylation enzymes.Methods in enzymology · 2020Article
- Article
- Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors.The Journal of antibiotics · 2019Review
- Kinetic Analyses of the Siderophore Biosynthesis Inhibitor Salicyl-AMS and Analogues as MbtA Inhibitors and Antimycobacterial Agents.Biochemistry · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Adenylation or adenylate-forming enzymes (AEs) are widely found in nature and are responsible for the activation of carboxylic acids to intermediate acyladenylates, which are mixed anhydrides of AMP. In a second reaction, AEs catalyze the transfer of the acyl group of the acyladenylate onto a nucleophilic amino, alcohol, or thiol group of an acceptor molecule leading to amide, ester, and thioester products, respectively. Mycobacterium tuberculosis encodes for more than 60 adenylating enzymes, many of which represent potential drug targets due to their confirmed essentiality or requirement for virulence. Several strategies have been used to develop potent and selective AE inhibitors including highthroughput screening, fragment-based screening, and the rationale design of bisubstrate inhibitors that mimic the acyladenylate. In this review, a comprehensive analysis of the mycobacterial adenylating enzymes will be presented with a focus on the identification of small molecule inhibitors. Specifically, this review will cover the aminoacyl tRNAsynthetases (aaRSs), MenE required for menaquinone synthesis, the FadD family of enzymes including the fatty acyl- AMP ligases (FAAL) and the fatty acyl-CoA ligases (FACLs) involved in lipid metabolism, and the nonribosomal peptide synthetase adenylation enzyme MbtA that is necessary for mycobactin synthesis. Additionally, the enzymes NadE, GuaA, PanC, and MshC involved in the respective synthesis of NAD, guanine, pantothenate, and mycothiol will be discussed as well as BirA that is responsible for biotinylation of the acyl CoA-carboxylases.
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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.