Chemical and enzymatic oxidation of benzimidazoline-2-thiones: a dichotomy in the mechanism of peroxidase inhibition.


:Derivatives of imidazole-2-thiones block reactions catalyzed by thyroid peroxidase (TPX) and the closely related lactoperoxidase (LPX), and this property is used therapeutically to treat hyperthyroidism. The reactions of a series of benzimidazoline-2-thiones with chemical and enzymatic oxidants were investigated to probe systematically the mechanism of inhibition. Oxidation of benzimidazoline-2-thione (I) and 1-methylbenzimidazoline-2-thione (II) with 3-chloroperbenzoic acid (PBA) yielded reaction products and stoichiometry consistent with benzimidazole-2-sulfenic acids as reactive intermediates. The N,N'-disubstituted nature of 1,3-dimethylbenzimidazoline-2-thione (III) precludes sulfenic acid formation by tautomerization, and the oxidation of III with PBA yielded products and stoichiometry that were consistent with a benzimidazole-2-sulfonyl ylide as the reactive intermediate. I and II are suicide inhibitors of LPX and TPX, but III was found to inhibit only peroxidase-catalyzed iodination reactions by an alternate substrate mechanism. These results provide support for the hypothesis that imidazole-2-sulfenic acids are important reactive intermediates in the suicide inactivation of TPX and LPX and relate the chemical reactivity of the inhibitor with both the potency and mechanism of inhibition. These results suggest that 1,3-disubstituted thiourea derivatives represent a new class of potential antihyperthyroid drugs that block TPX-catalyzed tyrosine iodination but do not cause irreversible enzyme inactivation.






Doerge DR,Decker CJ,Takazawa RS




Has Abstract


1993-01-12 00:00:00












  • Substrate activation by acyl-CoA dehydrogenases: transition-state stabilization and pKs of involved functional groups.

    abstract::The mechanism by which acyl-CoA dehydrogenases initiate catalysis was studied by using p-substituted phenylacetyl-CoAs (substituents-NO2, -CN, and CH3CO-), 3S-C8-, and 3'-dephospho-3S-C8CoA. These analogues lack a beta C-H and cannot undergo alpha,beta-dehydrogenation. Instead they deprotonate at alpha C-H at pH > or ...


    pub_type: 杂志文章


    authors: Vock P,Engst S,Eder M,Ghisla S

    更新日期:1998-02-17 00:00:00

  • Main chain and side chain dynamics of a heme protein: 15N and 2H NMR relaxation studies of R. capsulatus ferrocytochrome c2.

    abstract::A detailed characterization of the main chain and side chain dynamics in R. capsulatus ferrocytochrome c(2) derived from (2)H NMR relaxation of methyl group resonances is presented. (15)N relaxation measurements confirm earlier results indicating that R. capsulatus ferrocytochrome c(2) exhibits minor rotational anisot...


    pub_type: 杂志文章


    authors: Flynn PF,Bieber Urbauer RJ,Zhang H,Lee AL,Wand AJ

    更新日期:2001-06-05 00:00:00

  • Dyrk1A binds to multiple endocytic proteins required for formation of clathrin-coated vesicles.

    abstract::In spite of a nuclear targeting sequence, a substantial amount of dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk1A) is located within the cytoplasm of neurons. Analysis of fractionated rat brains revealed that the majority of Dyrk1A was in the postnuclear precipitate. The kinase in this fraction was ...


    pub_type: 杂志文章


    authors: Murakami N,Bolton D,Hwang YW

    更新日期:2009-10-06 00:00:00

  • Unfolding behavior of human alpha 1-acid glycoprotein is compatible with a loosely folded region in its polypeptide chain.

    abstract::The unfolding of human plasma alpha 1-acid glycoprotein (AGP) induced by heat or guanidine hydrochloride was studied under equilibrium conditions. In thermal unfolding, an intermediate state was detected by the appearance of unusual positive difference absorption bands in the 287-295-nm region, which occurred at lower...


    pub_type: 杂志文章


    authors: Rojo-Domínguez A,Zubillaga-Luna R,Hernández-Arana A

    更新日期:1990-09-18 00:00:00

  • Redesign of cosubstrate specificity and identification of important residues for substrate binding to hChAT.

    abstract::In eukaryotes, choline acetyltransferase (ChAT) catalyzes the reversible formation of the neurotransmitter acetylcholine from choline and acetyl-CoA. ChAT belongs to a family of CoA-dependent enzymes that also includes the carnitine acyltransferases CrAT, CrOT, and CPTs. In contrast to CrOT and CPTs that are very acti...


    pub_type: 杂志文章


    authors: Green KD,Porter VR,Zhang Y,Garneau-Tsodikova S

    更新日期:2010-07-27 00:00:00

  • Effects of temperature and viscosity on R67 dihydrofolate reductase catalysis.

    abstract::R67 dihydrofolate reductase (DHFR) is a novel homotetrameric protein that possesses 222 symmetry and a single, voluminous active site pore. This symmetry poses numerous limitations on catalysis; for example, two dihydrofolate (DHF) molecules or two NADPH molecules, or one substrate plus one cofactor can bind. Only the...


    pub_type: 杂志文章


    authors: Chopra S,Lynch R,Kim SH,Jackson M,Howell EE

    更新日期:2006-05-30 00:00:00

  • Toward engineering the stability and hemin-binding properties of microsomal cytochromes b5 into rat outer mitochondrial membrane cytochrome b5: examining the influence of residues 25 and 71.

    abstract::As part of a larger effort to engineer the stability and hemin-binding properties of microsomal (Mc) cytochromes b(5) into rat liver outer mitochondrial membrane (OM) cytochrome (cyt) b(5), several mutants of rat OM cyt b(5) were prepared to study the effect of gradual and complete elimination of two extended hydropho...


    pub_type: 杂志文章


    authors: Cowley AB,Altuve A,Kuchment O,Terzyan S,Zhang X,Rivera M,Benson DR

    更新日期:2002-10-01 00:00:00

  • Mechanistic studies on transcriptional coactivator protein arginine methyltransferase 1.

    abstract::Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to the guanidinium group of arginine residues in a number of important cell signaling proteins. PRMT1 is the founding member of this family, and its activity appears to be dysregulated in heart disease an...


    pub_type: 杂志文章


    authors: Rust HL,Zurita-Lopez CI,Clarke S,Thompson PR

    更新日期:2011-04-26 00:00:00

  • Subunit affinities and stoichiometries of the human papillomavirus type 11 E1:E2:DNA complex.

    abstract::The association between the papillomavirus E1 and E2 proteins is an important regulatory interaction, imparting coordinated control of viral transcription and replication. Using fluorescence polarization, we have characterized the interactions between HPV-11 E1, HPV-11 E2, and DNA in solution at equilibrium. For these...


    pub_type: 杂志文章


    authors: Chao SF,Rocque WJ,Daniel S,Czyzyk LE,Phelps WC,Alexander KA

    更新日期:1999-04-06 00:00:00

  • A new method for extraction of iron-molybdenum cofactor (FeMoco) from nitrogenase adsorbed to DEAE-cellulose. 2. Solubilization of FeMoco in a wide range of organic solvents.

    abstract::While the iron-molybdenum cofactor (FeMoco) of nitrogenase, a constituent of the active site for nitrogen reduction, can be extracted into N-methylformamide (NMF) and pyrrollidinone, the inability to solubilize it in any other organic solvents has hampered further understanding of its structure and chemical properties...


    pub_type: 杂志文章


    authors: Wink DA,McLean PA,Hickman AB,Orme-Johnson WH

    更新日期:1989-11-28 00:00:00

  • Characterization of the N-terminal and C-terminal domains of human apolipoprotein(a): relevance to fibrin binding.

    abstract::The structural domains of human apolipoprotein(a) (apo(a)) in the lipoprotein(a) (Lp(a)) particle have been recently investigated by limited proteolysis [Huby, T., Doucet, C., Dieplinger, H., Chapman, J., & Thillet, J. (1994) Biochemistry 33, 3335-3341]. We have shown that apo(a) can be cleaved into two structural dom...


    pub_type: 杂志文章


    authors: Huby T,Schröder W,Doucet C,Chapman J,Thillet J

    更新日期:1995-06-06 00:00:00

  • The vitelline envelope of eggs from the giant keyhole limpet Megathura crenulata. II. Products formed by lysis with sperm enzymes and dithiothreitol.

    abstract::The egg vitelline envelope of the marine invertebrate, Megathura crenulata, was lyzed either by sperm lysins A, B, C or by dithiothreitol. In each case the lysis mixture consisted of two major fractions, I and II, that could be separated by hydroxylapatite chromatography and had different electrophoretic mobilities on...


    pub_type: 杂志文章


    authors: Heller E,Raftery MA

    更新日期:1976-03-23 00:00:00

  • A novel delta(3),delta(2)-enoyl-CoA isomerase involved in the biosynthesis of the cyclohexanecarboxylic acid-derived moiety of the polyketide ansatrienin A.

    abstract::The side chain of the antifungal polyketide ansatrienin A produced by Streptomyces collinus contains a cyclohexanecarboxylic acid (CHC) derived moiety. This CHC in the coenzyme A activated form (CHC-CoA) is derived from shikimic acid via a pathway in which the penultimate step is the isomerization of 2-cyclohexenylcar...


    pub_type: 杂志文章


    authors: Patton SM,Cropp TA,Reynolds KA

    更新日期:2000-06-27 00:00:00

  • Entrapment of Water at the Transmembrane Helix-Helix Interface of Quiescin Sulfhydryl Oxidase 2.

    abstract::Little is known about how a membrane can regulate interactions between transmembrane helices. Here, we show that strong self-interaction of the transmembrane helix of human quiescin sulfhydryl oxidase 2 rests on a motif of conserved amino acids comprising one face of the helix. Atomistic molecular dynamics simulations...


    pub_type: 杂志文章


    authors: Ried CL,Scharnagl C,Langosch D

    更新日期:2016-03-08 00:00:00

  • Structure of human transferrin receptor oligosaccharides: conservation of site-specific processing.

    abstract::The human transferrin receptor (TfR) has three N-linked oligosaccharides. A combination of site-directed mutagenesis and carbohydrate and protein chemistry was used to characterize the structures of the N-linked oligosaccharides and to map their locations. We find that the type of oligosaccharide at each position was ...


    pub_type: 杂志文章


    authors: Hayes GR,Williams AM,Lucas JJ,Enns CA

    更新日期:1997-04-29 00:00:00

  • C5 cytosine methylation at CpG sites enhances sequence selectivity of mitomycin C-DNA bonding.

    abstract::We have established that UvrABC nuclease is equally efficient in cutting mitomycin C (MC)-DNA monoadducts formed at different sequences and that the degree of UvrABC cutting represents the extent of drug-DNA bonding. Using this method we determined the effect of C5 cytosine methylation on the DNA monoalkylation by MC ...


    pub_type: 杂志文章


    authors: Li VS,Reed M,Zheng Y,Kohn H,Tang M

    更新日期:2000-03-14 00:00:00

  • Nuclear magnetic resonance spectroscopy and molecular modeling reveal that different hydrogen bonding patterns are possible for G.U pairs: one hydrogen bond for each G.U pair in r(GGCGUGCC)(2) and two for each G.U pair in r(GAGUGCUC)(2).

    abstract::G.U pairs occur frequently and have many important biological functions. The stability of symmetric tandem G.U motifs depends both on the adjacent Watson-Crick base pairs, e.g., 5'G > 5'C, and the sequence of the G.U pairs, i.e., 5'-UG-3' > 5'-GU-3', where an underline represents a nucleotide in a G.U pair [Wu, M., Mc...


    pub_type: 杂志文章


    authors: Chen X,McDowell JA,Kierzek R,Krugh TR,Turner DH

    更新日期:2000-08-01 00:00:00

  • Photochemical cross-linking of tRNA1Arg to the 30S ribosomal subunit using aryl azide reagents attached to the anticodon loop.

    abstract::The 2-thiocytidine residue at position 32 of tRNA1Arg from Escherichia coli was modified specifically with three photoaffinity reagents of different lengths, and the corresponding N-acetylarginyl-tRNA1Arg derivatives were cross-linked to the P site of E. coli 70S ribosomes by irradiation. Covalent attachment was depen...


    pub_type: 杂志文章


    authors: Chen JK,Franke LA,Hixson SS,Zimmermann RA

    更新日期:1985-08-27 00:00:00

  • Functional characterization of the secondary actin binding site of myosin II.

    abstract::The role of the interaction between actin and the secondary actin binding site of myosin (segment 565-579 of rabbit skeletal muscle myosin, referred to as loop 3 in this work) has been studied with proteolytically generated smooth and skeletal muscle myosin subfragment 1 and recombinant Dictyostelium discoideum myosin...


    pub_type: 杂志文章


    authors: Van Dijk J,Furch M,Lafont C,Manstein DJ,Chaussepied P

    更新日期:1999-11-16 00:00:00

  • Properties of membrane-inserted protein kinase C.

    abstract::Protein kinase C (PKC) interacted with phospholipid vesicles in a calcium-dependent manner and produced two forms of membrane-associated PKC: a reversibly bound form and a membrane-inserted form. The two forms of PKC were isolated and compared with respect to enzyme stability, cofactor requirements, and phorbol ester ...


    pub_type: 杂志文章


    authors: Bazzi MD,Nelsestuen GL

    更新日期:1988-10-04 00:00:00

  • Crystal structure of the petal death protein from carnation flower.

    abstract::Expression of the PSR132 protein from Dianthus caryophyllus (carnation, clover pink) is induced in response to ethylene production associated with petal senescence, and thus the protein is named petal death protein (PDP). Recent work has established that despite the annotation of PDP in sequence databases as carboxyph...


    pub_type: 杂志文章


    authors: Teplyakov A,Liu S,Lu Z,Howard A,Dunaway-Mariano D,Herzberg O

    更新日期:2005-12-20 00:00:00

  • Hemes a and a3 environments of plant cytochrome c oxidase.

    abstract::The structures of hemes a and a3 of maize and wheat germ cytochrome c oxidase were investigated by resonance Raman spectroscopy. Comparison between the plant and mammalian cytochrome oxidases revealed that (i) the vinyl groups associated with hemes a and a3 vibrate at higher frequencies in the plant enzyme than in the...


    pub_type: 杂志文章


    authors: de Paula JC,Peiffer WE,Ingle RT,Centeno JA,Ferguson-Miller S,Babcock GT

    更新日期:1990-09-18 00:00:00

  • Reaction of nitric oxide with the turnover intermediates of cytochrome c oxidase: reaction pathway and functional effects.

    abstract::The reactions of nitric oxide (NO) with the turnover intermediates of cytochrome c oxidase were investigated by combining amperometric and spectroscopic techniques. We show that the complex of nitrite with the oxidized enzyme (O) is obtained by reaction of both the "peroxy" (P) and "ferryl" (F) intermediates with stoi...


    pub_type: 杂志文章


    authors: Giuffrè A,Barone MC,Mastronicola D,D'Itri E,Sarti P,Brunori M

    更新日期:2000-12-19 00:00:00

  • Resonance Raman and electronic absorption spectral studies of some beta-(2-furyl)acryloylglyceraldehyde-3-phosphate dehydrogenases.

    abstract::Electronic absorption and resonance Raman spectra, together with rates of arsenolysis, are used to show that the acylated subunits of the rabbit furylacryloylglyceraldehyde-3-phosphate dehydrogenase (FA-rabbit enzyme), but not the FA-sturgeon enzyme, exist as a mixed population of at least two forms. One form of the F...


    pub_type: 杂志文章


    authors: Storer AC,Phelps DJ,Carey PR

    更新日期:1981-06-09 00:00:00

  • Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines.

    abstract::Quinone oxidoreductase 2 (QR2) purified from human red blood cells was recently shown to be a potential target of the quinoline antimalarial compounds [Graves et al., (2002) Mol. Pharmacol. 62, 1364]. QR2 catalyzes the two-electron reduction of menadione via the oxidation of N-alkylated or N-ribosylated nicotinamides....


    pub_type: 杂志文章


    authors: Kwiek JJ,Haystead TA,Rudolph J

    更新日期:2004-04-20 00:00:00

  • Conserved phosphoprotein interaction motif is functionally interchangeable between ataxin-7 and arrestins.

    abstract::Olivopontocerebellar atrophy with retinal degeneration is a hereditary neurodegenerative disorder that belongs to the subtype II of the autosomal dominant cerebellar ataxias and is characterized by early-onset cerebellar and macular degeneration preceded by diagnostically useful tritan colorblindness. The gene mutated...


    pub_type: 杂志文章


    authors: Mushegian AR,Vishnivetskiy SA,Gurevich VV

    更新日期:2000-06-13 00:00:00

  • Kinetic analysis of product inhibition in human manganese superoxide dismutase.

    abstract::Manganese superoxide dismutase (MnSOD) cycles between the Mn(II) and Mn(III) states during the catalyzed disproportionation of O(2)(*-), a catalysis that is limited at micromolar levels of superoxide by a peroxide-inhibited complex with the metal. We have investigated the role in catalysis and inhibition of the conser...


    pub_type: 杂志文章


    authors: Hearn AS,Stroupe ME,Cabelli DE,Lepock JR,Tainer JA,Nick HS,Silverman DN

    更新日期:2001-10-09 00:00:00

  • Low permeability of liposomal membranes composed of bipolar tetraether lipids from thermoacidophilic archaebacterium Sulfolobus acidocaldarius.

    abstract::The physical origin of the extremely high thermal stability of tetraether liposomes composed of the polar lipid fraction E (PLFE) from the thermoacidophilic archaebacterium Sulfolobus acidocaldarius has been investigated. The leakage rate of trapped 5, 6-carboxyfluorescein (5(6)CF) and the proton permeability in PLFE ...


    pub_type: 杂志文章


    authors: Komatsu H,Chong PL

    更新日期:1998-01-06 00:00:00

  • Crotonase-catalyzed beta-elimination is concerted: a double isotope effect study.

    abstract::Determining the sequence of bond cleavages, and consequently the nature of intermediates, in enzyme-catalyzed reactions is a major goal of mechanistic enzymology. When significant primary isotope effects on V/K are observed for two different bond cleavages, both bonds may be broken in the same transition state or they...


    pub_type: 杂志文章


    authors: Bahnson BJ,Anderson VE

    更新日期:1991-06-18 00:00:00

  • Phospholipid spin probes measure the effects of ethanol on the molecular order of liver microsomes.

    abstract::Ethanol, in vitro, is known to perturb the molecular order of the phospholipids in biological membranes, while chronic ethanol exposure, in vivo, leads to resistance to disordering. Such changes have usually been measured by electron spin resonance, utilizing fatty acid spin probes. The use of such probes is controver...


    pub_type: 杂志文章


    authors: Taraschi TF,Wu A,Rubin E

    更新日期:1985-12-03 00:00:00