ArticleCommunications biology2023
Targeting Enterococcus faecalis HMG-CoA reductase with a non-statin inhibitor.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Drug-microbiome-host interactions: antimicrobial effects of non-antibiotic compounds.Nature reviews. Gastroenterology & hepatology · 2026Review
- A cofactor-promiscuous HMGR from the Lyme disease pathogen illuminates diversity in bacterial isoprenoid biosynthesis.Protein science : a publication of the Protein Society · 2026Article
- A cofactor-promiscuous HMGR from the Lyme disease pathogen illuminates diversity in bacterial isoprenoid biosynthesis.bioRxiv : the preprint server for biology · 2026Article
- Improving Cofactor Promiscuity of HMG-CoA Reductase fromBiomolecules · 2025Article
- Cryo-EM structures of apo and atorvastatin-bound human 3-hydroxy-3-methylglutaryl-coenzyme A reductase.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Production of the Sesquiterpene Bisabolene From One- and Two-Carbon Compounds in Engineered Methanosarcina acetivorans.Microbial biotechnology · 2025Article
- Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation.ACS central science · 2025Review
- Targeting the autophagy-miRNA axis in prostate cancer: toward novel diagnostic and therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- pH-dependent reaction triggering in PmHMGR crystals for time-resolved crystallography.Biophysical journal · 2024Article
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- The Effects of Tocotrienol on Gut Microbiota: A Scoping Review.Life (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
HMG-CoA reductase (HMGR), a rate-limiting enzyme of the mevalonate pathway in Gram-positive pathogenic bacteria, is an attractive target for development of novel antibiotics. In this study, we report the crystal structures of HMGR from Enterococcus faecalis (efHMGR) in the apo and liganded forms, highlighting several unique features of this enzyme. Statins, which inhibit the human enzyme with nanomolar affinity, perform poorly against the bacterial HMGR homologs. We also report a potent competitive inhibitor (Chembridge2 ID 7828315 or compound 315) of the efHMGR enzyme identified by a high-throughput, in-vitro screening. The X-ray crystal structure of efHMGR in complex with 315 was determined to 1.27 Å resolution revealing that the inhibitor occupies the mevalonate-binding site and interacts with several key active site residues conserved among bacterial homologs. Importantly, 315 does not inhibit the human HMGR. Our identification of a selective, non-statin inhibitor of bacterial HMG-CoA reductases will be instrumental in lead optimization and development of novel antibacterial drug candidates.
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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.