ArticleThe Journal of biological chemistry2016
New Insight into the Catalytic Mechanism of Bacterial MraY from Enzyme Kinetics and Docking Studies.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
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- TunR2, a novel mode-of-action tunicamycin-type antibiotic: Pharmacokinetics in C57BL/6 mouse and Holstein cattle.PloS one · 2025Article
- Proteome-wide bioinformatic annotation and functional validation of the monotopic phosphoglycosyl transferase superfamily.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Proteome-Wide Bioinformatic Annotation and Functional Validation of the Monotopic Phosphoglycosyl Transferase Superfamily.bioRxiv : the preprint server for biology · 2024Article
- Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives.ACS infectious diseases · 2024Review
- I am better than I look: genome based safety assessment of the probiotic Lactiplantibacillus plantarum IS-10506.BMC genomics · 2023Article
- The surprising structural and mechanistic dichotomy of membrane-associated phosphoglycosyl transferases.Biochemical Society transactions · 2021Review
- Structural and mechanistic themes in glycoconjugate biosynthesis at membrane interfaces.Current opinion in structural biology · 2019Review
- Cell-Wall Recycling of the Gram-Negative Bacteria and the Nexus to Antibiotic Resistance.Chemical reviews · 2018Review
- How Four Scientists Integrate Thermodynamic and Kinetic Theory, Context, Analogies, and Methods in Protein-Folding and Dynamics Research: Implications for Biochemistry Instruction.CBE life sciences education · 2018Article
- Bacillus subtilis MraY in detergent-free system of nanodiscs wrapped by styrene-maleic acid copolymers.PloS one · 2018Article
- Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Membrane Steps of Bacterial Cell Wall Synthesis as Antibiotic Targets.Antibiotics (Basel, Switzerland) · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospho-MurNAc-pentapeptide translocase (MraY) catalyzes the synthesis of Lipid I, a bacterial peptidoglycan precursor. As such, MraY is essential for bacterial survival and therefore is an ideal target for developing novel antibiotics. However, the understanding of its catalytic mechanism, despite the recently determined crystal structure, remains limited. In the present study, the kinetic properties of Bacillus subtilis MraY (BsMraY) were investigated by fluorescence enhancement using dansylated UDP-MurNAc-pentapeptide and heptaprenyl phosphate (C35-P, short-chain homolog of undecaprenyl phosphate, the endogenous substrate of MraY) as second substrate. Varying the concentrations of both of these substrates and fitting the kinetics data to two-substrate models showed that the concomitant binding of both UDP-MurNAc-pentapeptide-DNS and C35-P to the enzyme is required before the release of the two products, Lipid I and UMP. We built a model of BsMraY and performed docking studies with the substrate C35-P to further deepen our understanding of how MraY accommodates this lipid substrate. Based on these modeling studies, a novel catalytic role was put forward for a fully conserved histidine residue in MraY (His-289 in BsMraY), which has been experimentally confirmed to be essential for MraY activity. Using the current model of BsMraY, we propose that a small conformational change is necessary to relocate the His-289 residue, such that the translocase reaction can proceed via a nucleophilic attack of the phosphate moiety of C35-P on bound UDP-MurNAc-pentapeptide.
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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.