ArticleNature2016
Structural insights into inhibition of lipid I production in bacterial cell wall synthesis.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 122 citations in OpenAlex.
- Structures of Bacterial and Human Phosphoglycosyltransferases Bound to a Common Inhibitor Inform Selective Therapeutics.ACS chemical biology · 2026Article
- In Silico Identification of Natural-Product Aromatase (CYP19A1) Inhibitors via Integrated Molecular Docking and QSAR Modelling.Bioinformatics and biology insights · 2026Article
- 1,2,4-Triazole-Based First-in-Class Non-Nucleoside Inhibitors of the Bacterial Enzyme MraY.ACS bio & med chem Au · 2025Article
- Structures of bacterial and human phosphoglycosyltransferases bound to a common inhibitor inform selective therapeutics.bioRxiv : the preprint server for biology · 2025Article
- Recent Advances and Future Prospects in Biological-Membrane-Targeted Polymers.Polymer science & technology (Washington, D.C.) · 2025Review
- Article
- Computational prediction of CNP0387675 as a non-nucleoside inhibitor of MraY, from natural product-based multi-template screening againstFrontiers in microbiology · 2025Article
- Development of a natural product optimization strategy for inhibitors against MraY, a promising antibacterial target.Nature communications · 2024Article
- The MraY Inhibitor Muraymycin D2 and Its Derivatives Induce Enlarged Cells in Obligate IntracellularAntibiotics (Basel, Switzerland) · 2024Article
- Uridine Bisphosphonates Differentiate Phosphoglycosyl Transferase Superfamilies.Journal of the American Chemical Society · 2024Article
- The fall of the mycobacterial cell wall: interrogating peptidoglycan synthesis for novel anti-TB agents.PeerJ · 2024Review
- Integrated Transcriptomic and Metabolomic Mapping Reveals the Mechanism of Action of Ceftazidime/Avibactam against Pan-Drug-ResistantACS infectious diseases · 2023Article
- Biosynthesis and Genome Mining Potentials of Nucleoside Natural Products.Chembiochem : a European journal of chemical biology · 2023Article
- The mechanism of the phage-encoded protein antibiotic from ΦX174.Science (New York, N.Y.) · 2023Article
- Structure-Based Insight on the Mechanism of N-Glycosylation Inhibition by Tunicamycin.Molecules and cells · 2023Review
- Synthesis of an Antimicrobial Enterobactin-Muraymycin Conjugate for Improved Activity Against Gram-Negative Bacteria.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- The challenges and opportunities of developing small molecule inhibitors of MraY.Annual reports in medicinal chemistry · 2023Article
- Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY.Nature communications · 2022Article
- Intermolecular Interactions of Nucleoside Antibiotic Tunicamycin with On-Target MraYACS omega · 2022Article
- New MraYAntibiotics (Basel, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Antibiotic-resistant bacterial infection is a serious threat to public health. Peptidoglycan biosynthesis is a well-established target for antibiotic development. MraY (phospho-MurNAc-pentapeptide translocase) catalyses the first and an essential membrane step of peptidoglycan biosynthesis. It is considered a very promising target for the development of new antibiotics, as many naturally occurring nucleoside inhibitors with antibacterial activity target this enzyme. However, antibiotics targeting MraY have not been developed for clinical use, mainly owing to a lack of structural insight into inhibition of this enzyme. Here we present the crystal structure of MraY from Aquifex aeolicus (MraYAA) in complex with its naturally occurring inhibitor, muraymycin D2 (MD2). We show that after binding MD2, MraYAA undergoes remarkably large conformational rearrangements near the active site, which lead to the formation of a nucleoside-binding pocket and a peptide-binding site. MD2 binds the nucleoside-binding pocket like a two-pronged plug inserting into a socket. Further interactions it makes in the adjacent peptide-binding site anchor MD2 to and enhance its affinity for MraYAA. Surprisingly, MD2 does not interact with three acidic residues or the Mg(2+) cofactor required for catalysis, suggesting that MD2 binds to MraYAA in a manner that overlaps with, but is distinct from, its natural substrate, UDP-MurNAc-pentapeptide. We have determined the principles of MD2 binding to MraYAA, including how it avoids the need for pyrophosphate and sugar moieties, which are essential features for substrate binding. The conformational plasticity of MraY could be the reason that it is the target of many structurally distinct inhibitors. These findings can inform the design of new inhibitors targeting MraY as well as its paralogues, WecA and TarO.
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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.