Disease relevance of p-Chloromercuribenzoic acid

• Cell-free extracts of E. coli strains hosting the thiol-beta-lactamase gene possess a p-chloromercuribenzoate-sensitive beta-lactamase activity [1].
• Challenge of human or murine melanoma cells with sodium arsenite, heavy metals (Zn2+, Cu2+ and Cd2+), or thiol-reactive agents (p-chloromercuribenzoate and iodoacetamide) induced the synthesis of four stress proteins with molecular masses of 100, 90, 72 (a doublet), and 32 (human) or 34 (murine) kDa [2].
• Since the acyl-enzyme mechanism is not annihilated by pCMB derivatization, it is proposed that basically, and like all the other DD-peptidases/penicillin-binding proteins so far characterized, the Streptomyces K15 DD-peptidase is an active-site-serine enzyme [3].
• The H2-oxidation, H2-production and H-3H-exchange activities of the periplasmic hydrogenase from Desulfovibrio vulgaris (Hildenborough) were almost completely abolished by Hg(II) and the organic mercurials p-chloromercuribenzoate (pCMB) and p-hydroxymercuriphenylsulphonate [4].
• Among a wide range of potential selective agents examined, sodium p-hydroxymercuribenzoate successfully enriched for mutants of Synechocystis sp. strains PCC 6714 and 6803 defective in photosynthesis [5].

High impact information on p-Chloromercuribenzoic acid

• All converting activity in microsomes was found to be similar to that in granules in that it had a pH optimum near pH 5 and was inhibited by p-chloromercuribenzoate [6].
• The activity was purified 100-fold by ammonium sulfate precipitation, p-chloromercuribenzoate affinity chromatography, and chromatofocusing [7].
• Both polypeptides contain reactive thiol groups, but the rate of disruption of CRBP II-retinol complexes by p-chloromercuribenzoate is greater than that of CRBP-retinol [8].
• Transformed yeast cells expressing GFA1 demonstrated resistance to methylmercury but no resistance to p-chloromercuribenzoate, a GFAT inhibitor [9].
• It is concluded that PCMB permeates through the substrate pathway of EmrE and covalently reacts with the two exposed residues, Cys-95 and Cys-41, but not with Cys-39, located on the opposite face of the helix relative to residue 41 [10].

Chemical compound and disease context of p-Chloromercuribenzoic acid

• With some hepatoma preparations, the NADH oxidase activity of hepatoma plasma membranes was stimulated rather than inhibited by PCMB, whereas with all preparations of hepatoma plasma membranes, NEM and DTNB stimulated the activity [11].
• In extracts from Anacystis and Anabaena 7119, H2-evolution and uptake activities were strongly inhibited by Cu2+, p-chloromercuribenzoate and HgCl2 suggesting that at least one functional SH-group is involved in catalysis by hydrogenase [12].
• We previously reported that copper efflux from C6 rat glioma cells was blocked by a brief exposure to sulfhydryl reagents p-chloromercuribenzoate (PCMB) and iodoacetamide as well as dicyclohexylcarbodiimide, suggesting the possible involvement of a Cu-transporting ATPase in the efflux mechanism [13].
• Selective cysteine-->serine replacements in p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens allow the unambiguous assignment of Cys211 as the site of modification by spin-labeled p-chloromercuribenzoate [14].
• The mushroom enzyme, that was sensitive to DFP, Z-Pro-prolinal, and Z-Gly-Pro-CH2Cl, but not to PCMB, were quite similar in characteristics to the Flavobacterium enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)[15]

Biological context of p-Chloromercuribenzoic acid

• Cytochrome c reduction was not inhibited by several mitochondrial respiratory chain inhibitors (azide, cyanide, and rotenone) but was sensitive to thiol-reactive agents (p-chloromercuribenzoate and monoiodo acetate) [16].
• Pretreatment of the enzyme with p-chloromercuribenzoate and 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) did not reduce the binding of [14-C]pyruvate suggesting no active site SH was involved in the pyruvate-enzyme linkage [17].
• Derivatization of the DD-peptidase by pCMB decreases the efficacy of the initial binding of the ester carbonyl donor Ac2-L-Lys-D-Ala-D-lactate to the enzyme (K), the rate of enzyme acylation by the donor (K+2) and the rate of enzyme deacylation (k+3) [3].
• Activation mechanism and modification kinetics of Chinese hamster dihydrofolate reductase by p-chloromercuribenzoate [18].
• These results indicate that catecholamine secretion due to p-chloromercuribenzoate occurs by Ca2+-dependent exocytosis [19].

Anatomical context of p-Chloromercuribenzoic acid

• Employing the perfused pancreas technique, the insulin-releasing action of p-chloromercuribenzoate was further enhanced by leucine [20].
• Oligomycin, which inhibits ATP-dependent calcium uptake of liver mitochondria, has a considerably lesser effect on calcium uptake of liver microsomes. p-Chloromercuribenzoate and mersalyl inhibit the liver microsomal calcium pump at levels as low as 10- minus 7 M [21].
• The reasons underlying reported discrepancies in the effects of ATP, ADP, adenosine 5'-[beta gamma-methylene]triphosphate, AMP + PPi, P-chloromercuribenzoate and F- on RNA efflux from isolated rat liver nuclei and on nuclear envelope nucleoside triphosphatase activity were investigated [22].
• [125I]CCK octapeptide binding was significantly reduced when gastric glands were pretreated with iodoacetamide (IA; 10 mM), p-chloromercuribenzoate (PCMB; 0.1 mM), or N-ethylmaleimide (NEM; 0.1 mM) at 24 C, but not by dithiothreitol (DTT; 1.0 mM) or dinitrothiobenzoic acid (DTNB; 10 mM) [23].
• Other SH reagents, PCMB, NEM and DTNB, were shown to be relatively weak inhibitors of GABA uptake into cultured astrocytes, suggesting that SH groups are not directly involved in the interaction between GABA and its transport carrier [24].

Associations of p-Chloromercuribenzoic acid with other chemical compounds

• The purified enzyme showed a pH optima of 7.4-7.8, Km approximately 4 microM for GDP-Man, approximately 2-fold activation by phosphatidylcholine, and a strong inhibition by sulfhydryl-selective reagents, N-ethylmaleimide and p-chloromercuribenzoate [25].
• Zn(II) stimulates the activity of both the active and PCMB-activated latent forms of HNC up to a concentration of 50-100 microM, after which it inhibits markedly [26].
• The carboxypeptidase B which converts the oxytocinyl peptides showed a fairly sharp pH dependence with an optimum of 5.5-6, was activated by cobalt ion, and was inhibited by cupric ion, EDTA, and a thiol protease inhibitor, p-chloromercuribenzoate [27].
• Effect of leucine on the pyridine nucleotide contents of islets and on the insulin released--interactions in vitro with methylene blue, thiol oxidants, and p-chloromercuribenzoate [20].
• The protein phosphatase activity was optimal at pH 7.5 and was inhibited by fluoride (50 mM), inorganic phosphate (50 mM), and p-chloromercuribenzoate (0.1 mM), but was insensitive to vanadate (1 mM) [28].

Gene context of p-Chloromercuribenzoic acid

• A functional analysis showed that Cu efflux was blocked by the sulfhydryl reagent p-chloromercuribenzoate (p-CMB), a potential inhibitor of Atp7a function [29].
• Esterase-16 is strongly inhibited by 10(-3) M p-chloromercuribenzoate, but not by 2 [30].
• In contrast, hydrogen peroxide and cysteine-specific reagents, DTNB, MTSEA, and PCMB, decreased the channel activity [31].
• In vivo and in vitro functional studies, under the influence of the MCT1 inhibitors, p-chloromercuribenzoate (pCMB) and p-chloromercuribenzoic acid (pCMBA), demonstrated significant inhibitory effect on acetate and propionate transport in the rumen [32].
• These two enzymes differed from each other as follows: (i) the concentrations of clavulanic acid required for 50% beta-lactamase inhibition were 31 mumol/L for one enzyme (E-SAL) and 9.4 mumol/L for the other (E-GUER); (ii) p-chloromercuribenzoate was a more active inhibitor of E-SAL then E-GUER [33].

Analytical, diagnostic and therapeutic context of p-Chloromercuribenzoic acid

• Titration of native and diamide-inactivated enzyme with p-chloromercuribenzoate revealed that only two sulfhydryl groups were involved in the formation of the disulfide cross-linkage across the subunits [34].
• Using homogenization conditions that preclude this proteolysis (low pH and the addition of the protease inhibitor p-chloromercuribenzoate) and immunoblotting as an assay for the protein, a procedure for the purification of ubiquitin from etiolated oat shoots was developed [35].
• The strong inhibitory action of phosphate ions on the reverse reaction [Voordouw et al. (1980) Eur. J. Biochem. 107, 337-344] is abolished after treatment with p-chloromercuribenzoate [36].
• Bronchial obstruction was measured by whole body plethysmography . PCMB, Cu, CuDTT , DTT and DMP inhibited AT, whereas Au and ZnDTT enhanced AT [37].
• Modified two-dimensional electrophoresis for identification and autoradiography of ribosomal proteins reacted with p-chloromercuribenzoate [38].

References