ArticleBiochemistry2012
Biochemical and structural basis for inhibition of Enterococcus faecalis hydroxymethylglutaryl-CoA synthase, mvaS, by hymeglusin.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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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.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Advances in microbial mevalonolactone production: from fermentative mevalonate accumulation to downstream lactonization.Engineering microbiology · 2026Review
- pH-dependent reaction triggering in PmHMGR crystals for time-resolved crystallography.Biophysical journal · 2024Article
- Mevalonate secretion is not mediated by a singular non-essential transporter inBiotechnology notes (Amsterdam, Netherlands) · 2024Article
- Biofilm Formation ofMicroorganisms · 2023Review
- Effects of medium chain triglycerides on hepatic fatty acid oxidation in clofibrate-fed newborn piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Article
- Tyrosine-targeted covalent inhibition of a tRNA synthetase aided by zinc ion.Communications biology · 2023Article
- Article
- Inhibition of Orbivirus Replication by Fluvastatin and Identification of the Key Elements of the Mevalonate Pathway Involved.Viruses · 2021Article
- Mono-/Bis-Alkenoic Acid Derivatives From an Endophytic FungusFrontiers in chemistry · 2021Article
- Isotopically Labeled Desthiobiotin Azide (isoDTB) Tags Enable Global Profiling of the Bacterial Cysteinome.Angewandte Chemie (International ed. in English) · 2020Article
- Computational Structural Biology ofFrontiers in oncology · 2018Review
- Prevention of Dietary-Fat-Fueled Ketogenesis Attenuates BRAF V600E Tumor Growth.Cell metabolism · 2017Article
- Anatomy of the β-branching enzyme of polyketide biosynthesis and its interaction with an acyl-ACP substrate.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- Article
- Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids.Diabetes · 2014Article
- The increasingly complex mechanism of HMG-CoA reductase.Accounts of chemical research · 2013Review
- Expression in Haloferax volcanii of 3-hydroxy-3-methylglutaryl coenzyme A synthase facilitates isolation and characterization of the active form of a key enzyme required for polyisoprenoid cell membrane biosynthesis in halophilic archaea.Journal of bacteriology · 2013Article
- Specificity in transition state binding: the Pauling model revisited.Biochemistry · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hymeglusin (1233A, F244, L-659-699) is established as a specific β-lactone inhibitor of eukaryotic hydroxymethylglutaryl-CoA synthase (HMGCS). Inhibition results from formation of a thioester adduct to the active site cysteine. In contrast, the effects of hymeglusin on bacterial HMG-CoA synthase, mvaS, have been minimally characterized. Hymeglusin blocks growth of Enterococcus faecalis. After removal of the inhibitor from culture media, a growth curve inflection point at 3.1 h is observed (vs 0.7 h for the uninhibited control). Upon hymeglusin inactivation of purified E. faecalis mvaS, the thioester adduct is more stable than that measured for human HMGCS. Hydroxylamine cleaves the thioester adduct; substantial enzyme activity is restored at a rate that is 8-fold faster for human HMGCS than for mvaS. Structural results explain these differences in enzyme-inhibitor thioester adduct stability and solvent accessibility. The E. faecalis mvaS-hymeglusin cocrystal structure (1.95 Å) reveals virtually complete occlusion of the bound inhibitor in a narrow tunnel that is largely sequestered from bulk solvent. In contrast, eukaryotic (Brassica juncea) HMGCS binds hymeglusin in a more solvent-exposed cavity.
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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.