Disease relevance of chloromethane

• A corrinoid-dependent catabolic pathway for growth of a Methylobacterium strain with chloromethane [1].
• The methylotrophic bacterium Hyphomicrobium chloromethanicum CM2 can utilize chloromethane (CH(3)Cl) as the sole carbon and energy source [2].
• Hyphomicrobium chloromethanicum CM2(T), an aerobic methylotrophic member of the alpha subclass of the class proteobacteria, can grow with chloromethane as the sole carbon and energy source [3].
• Modification of Bacillus subtilis elongation factor Tu by N-tosyl-L-phenylalanyl chloromethane abolishes its ability to interact with the 3'-terminal polynucleotide structure but not with the acyl bond in aminoacyl-tRNA [4].
• Chemical modification of this Cys81 in EF-Tu from Escherichia coli by N-tosyl-L-phenylalanine chloromethane [Jonák, J., Petersen, T. E., Clark, B. F. C. & Rychlík, I. (1982) FEBS Lett. 150, 485-488], and of homologous Cys residues in other bacterial EF-Tu, selectively blocks the binding of Xaa-tRNA [5].

High impact information on chloromethane

• Sequence analysis, mutant properties, and measurements of enzyme activity in cell-free extracts allowed the definition of a multistep pathway for the conversion of chloromethane to formate [1].
• Finally, an octapeptidyl chloromethane derivative proved to be a potent irreversible inhibitor of either PC1 and ruin [6].
• Soil bacteria are heavily exposed to environmental methylating agents such as methylchloride and may have special requirements for repair of alkylation damage on DNA [7].
• We propose that the lower polarity of the chymotrypsin active site relative to that of the subtilisin active site explains why the oxyanion pKa is higher and more sensitive to the type of chloromethane inhibitor used in the chymotrypsin derivatives than in the subtilisin derivatives [8].
• Thrombomodulin increased the rate of inactivation of thrombin by two peptidyl chloromethane inhibitors by a similar amount [9].

Chemical compound and disease context of chloromethane

• Chloromethane-induced genes define a third C1 utilization pathway in Methylobacterium chloromethanicum CM4 [10].

Biological context of chloromethane

• The kinetics for the inactivation of thrombin (EC 3.4.21.5) by a series of peptides containing C-terminal arginyl chloromethane in the presence of substrate were determined [11].
• (2) A 2-3 fold increase in the binding constant (KI) of a tripeptidyl chloromethane inhibitor was observed, but the inactivation rate constant (k i) was the same, which indicated that the nucleophilicity of the active-site histidyl residue had not changed [12].
• The chloromethane-utilizing methylation system is absent in early growth but attains peak activity in the mid-growth phase after 72 h of incubation [13].
• Chloromethane utilization gene cluster from Hyphomicrobium chloromethanicum strain CM2(T) and development of functional gene probes to detect halomethane-degrading bacteria [3].
• For comparison, the amination of chloromethane by lithium dimethylamide and the reduction by borane, diborane, and borohydride ions were also examined [14].

Anatomical context of chloromethane

• Previous studies from this laboratory described the kinetic characteristics of the inhibition by tosylphenylalanine chloromethane (TosPheCH2Cl) on superoxide anion production by human neutrophils (PMN) stimulated with a phorbol ester (PMA) [15].
• We have radiolabeled the membranes of cells inactivated before or after phorbol ester stimulation, using either [3H]KBH4 reduction after reaction with unlabeled inactivator, or tritiated tosylphenylalanyl chloromethane [16].
• All-trans-retinoyl chloromethane is a potent irreversible inactivator of bovine opsin in retinal rod outer segments [17].
• The purpose of this study was to measure the distribution of a radiolabeled drug [3H]bicuculline methylchloride ([3H]BMC) following microinjection into the supraoptic nuclei (SON) and the dorsal hypothalamus of conscious rats [18].
• 3. In liver microsomes from both sexes of mouse, the rates of oxidation of chloromethane and chlorzoxazone were two-fold higher than in kidney microsomes from the male, however, no sex differences in the rates of oxidation were observed [19].

Associations of chloromethane with other chemical compounds

• Overall, these results suggest that tosyl-lysyl chloromethane modulates several properties of the glucocorticoid-receptor complex, that tosyl-lysyl chloromethane effects resemble those of molybdate, and that a serine proteinase(s) could be involved in the mechanism of glucocorticoid-receptor complex activation into a nuclear binding form [20].
• Although the biochemical role of the chloromethane-dependent methylation system in metabolism is not known, one possible function could be the regeneration of veratryl alcohol degraded by the attack of lignin peroxidase [13].
• The reduction of chloromethane by LAB occurred most readily from a conformation that allowed coordination of the lithium atom to the chloride leaving group, and the most favorable amination pathway occurred by a backside attack of the nitrogen nucleophile on chloromethane [14].
• Two proteins, CmuA and CmuB, were previously purified and shown to catalyze the dehalogenation of chloromethane and the vitamin B12-mediated transfer of the methyl group of chloromethane to tetrahydrofolate [10].
• While CmuB was previously shown to possess methylcobalamin:tetrahydrofolate methyltransferase activity, sequence analysis indicated that CmuA represented a novel and so far unique two-domain methyltransferase/corrinoid-binding protein involved in methyl transfer from chloromethane to a corrin moiety [21].

Gene context of chloromethane

• In order to identify physiological activators of proteinase-activated receptor-2 (PAR-2), a peptide chloromethane inhibitor (biotinyl-Ser-Lys-Gly-Arg-CH2Cl) based on the cleavage site for activation of PAR-2 was synthesised and tested with 12 trypsin-like serine proteinases [22].
• Affinity labeling of bovine opsin by trans-retinoyl chloromethane [17].
• Tosyl-lysyl chloromethane alters glucocorticoid-receptor complex nuclear binding and physical properties [20].
• The major proteinase has pH optimum 8, a Ca2+-dependence maximum of 1 mM, and was inhibited by serine-proteinase inhibitors, especially tetrapeptidyl chloromethane derivatives with hydrophobic residues at the P-1 site [23].
• Modification of B. subtilis EF-Tu by N-tosyl-L-phenylalanyl chloromethane destroyed its ability to promote protein synthesis and resulted in selective dissociation of the two binding activities of the protein for aminoacyl-tRNA [4].

Analytical, diagnostic and therapeutic context of chloromethane

• PCR primers were developed for successful amplification of cmuA genes from newly isolated chloromethane utilizers and enrichment cultures [3].
• The slope of toxicodynamics curves for depressed ChE increased about 3 times after treatment with Nef 7.5 mg/kg and pyratoxime methylchloride (2-PAM Cl) 50 mg/kg, compared with the untreated group, there was a higher significant difference (P<0.01) [24].

References