Isopentenyl Diphosphate Inhibition of Thiamin Diphosphate Enzymes, Especially Deoxyxylulose 5‐Phosphate Synthase
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چکیده
منابع مشابه
Activation of thiamin diphosphate in enzymes.
Activation of the coenzyme ThDP was studied by measuring the kinetics of deprotonation at the C2 carbon of thiamin diphosphate in the enzymes pyruvate decarboxylase, transketolase, pyruvate dehydrogenase complex, pyruvate oxidase, in site-specific mutant enzymes and in enzyme complexes containing coenzyme analogues by proton/deuterium exchange detected by 1H-NMR spectroscopy. The respective dep...
متن کاملTaxodione and arenarone inhibit farnesyl diphosphate synthase by binding to the isopentenyl diphosphate site.
We used in silico methods to screen a library of 1,013 compounds for possible binding to the allosteric site in farnesyl diphosphate synthase (FPPS). Two of the 50 predicted hits had activity against either human FPPS (HsFPPS) or Trypanosoma brucei FPPS (TbFPPS), the most active being the quinone methide celastrol (IC50 versus TbFPPS ∼ 20 µM). Two rounds of similarity searching and activity tes...
متن کاملNMR analysis of covalent intermediates in thiamin diphosphate enzymes.
Enzymic catalysis proceeds via intermediates formed in the course of substrate conversion. Here, we directly detect key intermediates in thiamin diphosphate (ThDP)-dependent enzymes during catalysis using (1)H NMR spectroscopy. The quantitative analysis of the relative intermediate concentrations allows the determination of the microscopic rate constants of individual catalytic steps. As demons...
متن کاملPotent Radical-Scavenging Activities of Thiamin and Thiamin Diphosphate
Various radical-scavenging activities of thiamin and thiamin diphosphate (TDP) were found in some in vitro experiments. Thiamin and TDP caused considerable suppressive effects on superoxide generation in hypoxanthine and xanthine oxidase system which was measured by a sensitive chemiluminescence method using 2-methyl-6-[p-methylphenyl]-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA), and thei...
متن کاملEnterococcus faecalis 3-hydroxy-3-methylglutaryl coenzyme A synthase, an enzyme of isopentenyl diphosphate biosynthesis.
Biosynthesis of the isoprenoid precursor isopentenyl diphosphate (IPP) proceeds via two distinct pathways. Sequence comparisons and microbiological data suggest that multidrug-resistant strains of gram-positive cocci employ exclusively the mevalonate pathway for IPP biosynthesis. Bacterial mevalonate pathway enzymes therefore offer potential targets for development of active site-directed inhib...
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ژورنال
عنوان ژورنال: The FASEB Journal
سال: 2015
ISSN: 0892-6638,1530-6860
DOI: 10.1096/fasebj.29.1_supplement.887.20