Abstract:
: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.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Doerge DR,Decker CJ,Takazawa RSdoi
10.1021/bi00052a009subject
Has Abstractpub_date
1993-01-12 00:00:00pages
58-65issue
1eissn
0006-2960issn
1520-4995journal_volume
32pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The unfolding and dissociation of the tetrameric enzyme fructose-1,6-bisphosphatase from pig kidney by guanidine hydrochloride have been investigated at equilibrium by monitoring enzyme activity, ANS binding, intrinsic (tyrosine) protein fluorescence, exposure of thiol groups, fluorescence of extrinsic probes (AEDANS,...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi034203m
更新日期:2003-06-17 00:00:00
abstract::Bacillus thuringiensis (Bt) insecticidal toxins bind to receptors on midgut epithelial cells of susceptible insects, and binding triggers biochemical events that lead to insect mortality. Recently, a 100-kDa aminopeptidase N (APN) was isolated from brush border membrane vesicles (BBMV) of Anopheles quadrimaculatus and...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi801181g
更新日期:2008-10-28 00:00:00
abstract::The nature of the putative general acid His187 in the reaction catalyzed by Escherichia coli uracil DNA glycosylase (UDG) was investigated using X-ray crystallography and NMR spectroscopy. The crystal structures of H187Q UDG, and its complex with uracil, have been solved at 1.40 and 1.60 A resolution, respectively. Th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9910880
更新日期:1999-09-14 00:00:00
abstract::Flavin-dependent histone demethylases catalyze the posttranslational oxidative demethylation of mono- and dimethylated lysine residues, producing formaldehyde and hydrogen peroxide in addition to the corresponding demethylated protein. In vivo, histone demethylase LSD1 (KDM1; BCH110) is a component of the multiprotein...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101776t
更新日期:2011-02-01 00:00:00
abstract::RecG is a DNA helicase involved in the repair of damage at a replication fork and catalyzes the reversal of the fork to a point beyond the damage in the template strand. It unwinds duplex DNA in reactions that are coupled to ATP hydrolysis. The kinetic mechanism of duplex DNA unwinding by RecG was analyzed using a qua...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0512851
更新日期:2005-12-27 00:00:00
abstract::The stereochemical problem involving a pro-pro-prochiral phosphorus center, the hydrolysis of adenosine 5'-monophosphate to adenosine and inorganic phosphate catalyzed by the venom 5'-nucleotidase, has been studied by use of chiral [16O, 17O, 18O]thiophosphates (Psi). (Rp)- and (Sp)-[alpha-18O1]Adenosine 5'-thiophosph...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00564a025
更新日期:1980-11-11 00:00:00
abstract::The repeating units of mouse, rat, and alpha-monkey satellites have been cloned. All three show properties that are characteristic of curved DNA: (i) their migration in polyacrylamide gels is slower than predicted from their sequences, and (ii) they appear as curved molecules when visualized by electron microscopy. Al...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00461a019
更新日期:1990-03-06 00:00:00
abstract::Introduction of a disulfide bond by site-directed mutagenesis was found to enhance the stability of subtilisin BPN' (EC 3.4.21.14) under a variety of conditions. The location of the new disulfide bond was selected with the aid of a computer program, which scored various sites according to the amount of distortion that...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00382a002
更新日期:1987-04-21 00:00:00
abstract::For expression in Saccharomyces cerevisiae the cDNA of the uncoupling protein (UCP) of brown adipose tissue from hamster has been isolated and used to transform yeast cells. Optimized expression conditions yielded 2% of mitochondrial protein as UCP. UCP was isolated, avoiding copurification of ADP/ATP carrier and pori...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970513r
更新日期:1997-07-08 00:00:00
abstract::Rhodanese bound to bacterial ribosomes as peptidyl-tRNA can be folded into an enzymatically active conformation by generating C-terminal extensions of the wild-type enzyme. Rhodanese was synthesized by coupled transcription/translation in a cell-free Escherichia coli system from plasmids containing the coding sequence...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00044a003
更新日期:1995-11-07 00:00:00
abstract::Human type beta 2 transforming growth factor (hTGF-beta 2) was purified from tamoxifen-supplemented, serum-free medium conditioned by the human prostatic adenocarcinoma cell line PC-3. The purification of hTGF-beta 2 was monitored in a growth inhibition assay and was achieved by batch purification on methylsilyl-contr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00383a002
更新日期:1987-05-05 00:00:00
abstract::Adenylosuccinate synthetase catalyzes the first committed step in the de novo biosynthesis of AMP, coupling L-aspartate and IMP to form adenylosuccinate. Km values of IMP and 2'-deoxy-IMP are nearly identical with each substrate supporting comparable maximal velocities. Nonetheless, the Km value for L-aspartate and th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0607498
更新日期:2006-09-26 00:00:00
abstract::Escherichia coli MutS protein, which is required for mismatch repair, has a slow ATPase activity that obeys Michalelis-Menten kinetics. At 37 degrees C, the steady-state turnover rate for ATP hydrolysis is 1.0 +/- 0.3 min(-1) per monomer equivalent with a K(m) of 33 +/- 6 microM. Hydrolysis is competitively inhibited ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi992286u
更新日期:2000-03-21 00:00:00
abstract::Elastin binding proteins from plasma membranes of elastin-producing cells were isolated by affinity chromatography on immobilized elastin peptides. Three proteins of 67, 61, and 55 kDa were released from the elastin resin by guanidine/detergent, soluble elastin peptides, synthetic peptide VGVAPG, or galactoside sugars...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00435a014
更新日期:1989-05-02 00:00:00
abstract::An allelic variant of the ouabain-insensitive rat kidney Na+,K(+)-ATPase alpha 1-isoform was identified by chance in a cDNA library. The variant differed from the wild-type rat kidney Na+,K(+)-ATPase by a single G to C base substitution in the cDNA, which on the amino acid level gave rise to a glutamine in place of th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00211a048
更新日期:1993-12-07 00:00:00
abstract::This study was undertaken to identify the alpha-helical domains of human apoE that mediate cellular cholesterol efflux and HDL assembly via ATP-binding cassette transporter A1 (ABCA1). The C-terminal (CT) domain (residues 222-299) of apoE was found to stimulate ABCA1-dependent cholesterol efflux in a manner similar to...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi602407r
更新日期:2007-03-13 00:00:00
abstract::The multicatalytic proteinase complex (MPC, proteasome) is composed of 28 subunits organized into four rings surrounding a water-filled canal. The catalytic centers face the inner canal confining protein substrates to an enclosed space. Experimental findings obtained with MPC from archaebacteria suggest that degradati...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi990826h
更新日期:1999-11-02 00:00:00
abstract::Neutral glycosphingolipids and gangliosides in rabbit thymus, spleen, bone marrow, and erythrocyte ghosts were analyzed by conventional chemical and enzymatic procedures and negative ion fast atom bombardment mass spectrometry (FABMS). Thymus gangliosides showed a characteristic composition. Major gangliosides compris...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00352a023
更新日期:1986-02-25 00:00:00
abstract::Resonances of the histidine region of human carbonic anhydrase B have been studied by proton magnetic resonance spectroscopy in the presence of seven sulfonamide inhibitors. Results of difference spectroscopy and observation of the C-2 resonance of an additional titratable histidine in some of these spectra suggest a ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00675a007
更新日期:1975-02-25 00:00:00
abstract::The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the reaction between shikimate 3-phosphate and phosphoenolpyruvate to form 5-enolpyruvylshikimate 3-phosphate, an intermediate in the shikimate pathway, which leads to the biosynthesis of aromatic amino acids. EPSPS exists in an open conformation...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi800134y
更新日期:2008-07-15 00:00:00
abstract::Autophagy, an essential eukaryotic homeostasis pathway, allows the sequestration of unwanted, damaged, or harmful cytoplasmic components in vesicles called autophagosomes, permitting subsequent lysosomal degradation and nutrient recycling. Autophagosome nucleation is mediated by class III phosphatidylinositol-3-kinase...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00246
更新日期:2016-08-02 00:00:00
abstract::The refined crystallographic structure of the "closed" conformation of chicken mitochondrial aspartate aminotransferase has been used as a template for the construction of models of the two Escherichia coli aminotransferases encoded by the tyrB and aspC genes. The main results are as follows: (1) Only minor changes ar...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00422a009
更新日期:1988-11-01 00:00:00
abstract::The light-induced global conformational change of photoactive yellow protein was directly observed by small-angle X-ray scattering (SAXS). The N-terminal 6, 15, or 23 amino acid residues were enzymatically truncated (T6, T15, or T23, respectively), and their near-UV intermediates were accumulated under continuous illu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0264768
更新日期:2002-11-19 00:00:00
abstract::In the presence of Ca2+ and calmodulin (CM), purified smooth muscle myosin light chain kinase (MLCKase) was found to undergo autophosphorylation at a rate that was about 200-fold slower than its catalytic activity. Up to 1.7 mol of phosphate were incorporated per mole of kinase. Lower levels of incorporation could be ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00037a025
更新日期:1995-09-19 00:00:00
abstract::The head of the P22 bacteriophage is interrupted by a unique dodecameric portal vertex that serves as a conduit for the entrance and exit of the DNA. Here, the in vitro unfolding/refolding processes of the portal protein of P22 were investigated at different temperatures (1, 25, and 37 degrees C) through the use of ur...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi700006d
更新日期:2007-06-26 00:00:00
abstract::Enterokinase has been isolated from the contents of bovine duodena and purified 1200-fold in 41% yield. The isolation procedure employed DEAE chromatography, affinity chromatography on immobilized p-aminobenzamidine, and gel filtration. The resultant pure enzyme exhibits a single band on sodium dodecyl sulfate gel ele...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00634a011
更新日期:1977-07-26 00:00:00
abstract::We have biochemically and kinetically characterized the polymerase and exonuclease activities of the third B-family polymerase (Dpo3) from the hyperthermophilic Crenarchaeon, Sulfolobus solfataricus (Sso). We have established through mutagenesis that despite incomplete sequence conservation, the polymerase and exonucl...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi201799a
更新日期:2012-03-06 00:00:00
abstract::Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent enzyme that catalyzes the transfer of a methyl group from glycine betaine (Bet) to homocysteine (Hcy) to form dimethylglycine (DMG) and methionine (Met). Previous studies in other laboratories have indicated that catalysis proceeds through the formati...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi049821x
更新日期:2004-05-11 00:00:00
abstract::The X-ray crystal structure of a salicylhydroxamic acid (SHA) inhibitory complex with human myeloperoxidase (MPO) has been determined at 2.3 A resolution. The aromatic ring of the inhibitor binds to a hydrophobic region at the entrance to the distal heme pocket between heme pyrrole ring D and the side chain of Arg 239...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960577m
更新日期:1996-08-20 00:00:00
abstract::Microfibrils having a diameter of 10-12 nm, found either in association with elastin or independently, are an important component of the extracellular matrix of many tissues. Because isolation of native proteins composing the microfibrils has proven difficult, information on structure/function relationships is limited...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00168a026
更新日期:1994-01-18 00:00:00