Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight monofunctional alkylating agents were examined for their ability to induce mutation in Salmonella typhimurium. The assay was carried out in S. typhimurium TA100 with the preincubation method. The SN1-type agents were more mutagenic than the SN2-type ones; besides, methylating agents exerted more mutagenic activity than ethylating ones. Those responses in the reversion assay were quite similar to the results obtained previously with the beta-galactosidase assay in Escherichia coli CSH26/pMCP1000 (alkA'-lacZ') as to the induction of the adaptive response. A good correlation was found between mutagenic potency in the reverse mutation assay and inducing potency in the beta-galactosidase assay.
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PMID:A straight correlation between mutagenic activity and beta-galactosidase activity induced by monofunctional alkylating agents. 138 Jun 69

17 monofunctional methanesulphonates of widely varying structures were investigated in the SOS chromotest using the E. coli strain PQ37. All compounds tested were positive in this assay. The monofunctional methanesulphonates in general possess low SOSiP values. Five of the compounds tested i.e. iBMS, NpMS, 2 PhPMS, PkMS and 1,3-DC12PMS (for abbreviations see Table 1) did not show increasing beta-galactosidase activity and both the positive induction factors and the positive SOSiP values resulted from the toxicity correction as performed according to Quillardet and Hofnung (1985). In general methanesulphonates with a higher SN1 reactivity, in particular the secondary compounds, showed clear genotoxic activities whereas those possessing low SN1 reactivities (primary compounds) induced a low SOS repair indicating that the alkylation of O-atoms in the DNA bases contributes more to the induction of SOS repair in strain PQ37 than N-alkylations. The only exception was methyl methanesulphonate (MMS) which possessed a very high SN2 reactivity but a rather low SN1 reactivity. It had the highest SOSiP value of all tested methanesulphonates. No dependence of the genotoxicity on the SN2 reactivity could be found in this series. In general the phenyl-substituted methanesulphonates showed higher SOSiP values, which is presumably due to their relatively high SN1 reactivities and their relatively long life times in aqueous systems. There is a clear relationship between SN1 reactivities and the SOSiP values: the SOSiP values increase with rising SN1 reactivities reaching a maximum at iPMS after which the genotoxicities decrease due to the decreasing life times. The compounds with very high SN1 reactivities also possess very high hydrolysis rates. A good correlation could be established between the mutagenicities in S. typhimurium TA100 and the SOS chromotest (strain PQ37). Only 4 small deviations from this correlation could be found. The reasons for these deviations are discussed.
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PMID:Genotoxicity of monofunctional methanesulphonates in the SOS chromotest as a function of alkylation mechanisms. A comparison with the mutagenicity in S. typhimurium TA100. 253 26

Seventeen monofunctional alkylmethanesulphonates of widely varying structures were investigated in the SOS Chromotest using the Escherichia coli strains PM21, PQ37 and GC4798. As a measure of the SOS-inducing activity, the beta-galactosidase enzyme units (Up/mumol) were determined. Strains PM21 and PQ37 gave similar results in spite of the presence of different genetic markers. In general, the SN1 type secondary compounds (O-alkylation) induced higher SOS repair than the SN2 type primary compounds (N-alkylation). However, methylmethanesulphonate exerted the highest SOS induction of all tested strains, presumably due to its extremely high SN2 reactivity. In general, strain GC4798, which lacks 3-alkyladenine-DNA glycosylases I and II, was more sensitive towards monofunctional alkylating compounds and in particular towards the SN2 type compounds. A good correlation was found between the SOS repair response in the E. coli strains PM21 and PQ37 and the mutagenicity in Salmonella typhimurium TA100. There was, however, little correspondence when comparing the two measures used for the SOS-inducing activity in this work, the SOSIP (SOS-inducing potency) and the specific beta-galactosidase activity (Up/mumol). This effect was explained by the different toxicity corrections used for the calculation of the two measures. Whereas for the SOSIP value the single constitutive enzyme alkaline phosphatase is used, for the Up/mumol the absorbance at 600 nm, which indicates the growth delay (overall toxicity), is utilized. The influence of the toxicity corrections is discussed in more detail.
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PMID:Induction of SOS repair by monofunctional methanesulphonates in various Escherichia coli strains. Structure-activity relationships in comparison with mutagenicity in Salmonella typhimurium. 254 87

We used alkA'-lacZ' and umuC'-lacZ' fused genes and determined the ability of various alkylating agents to induce adaptive and SOS responses. The degree of induction of expression of these genes was quantitatively measured by a simple colorimetric assay of beta-galactosidase activity. SN1 type methylating agents, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, were more effective inducers for the alkA than for the umuC system, while SN1 type ethylating agents, such as N-ethyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea, were more potent inducers for the umuC than for the alkA system. Similar but less striking effects on the two systems were obtained with SN2 type alkylating agents.
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PMID:Ability of various alkylating agents to induce adaptive and SOS responses: a study with lacZ fusion. 299 77

Oxygen-18 leaving group kinetic isotope effects (KIEs) have been determined on both Vmax (V) and Vmax/Km (V/K) for the beta-galactosidase-catalyzed hydrolysis of p-nitrophenyl beta-D-galactoside (I) and 2,4-dinitrophenyl beta-D-galactoside (II). The former substrate exhibits KIEs of 1.022 +/- 0.002 and 1.014 +/- 0.003 on V and V/K, respectively, while corresponding KIEs for the latter are 1.002 +/- 0.0009 and 1.030 +/- 0.003. These results indicate that bond scission is largely rate determining for I but not for II at substrate saturation. The first irreversible step for both substrates must involve cleavage of the bond to the nitrophenyl leaving group. The mechanism proposed for this reaction is characterized by two parallel pathways for substrate hydrolysis. The predominant route for all but the most reactive substrates involves a SN2 nucleophilic displacement of aglycon by the enzyme to yield a covalent galactosyl-enzyme which in turn is hydrolyzed via a nucleophilic attach by water. The most reactive substrates (e.g., II) from transiently an enzyme-bound galactosyl oxo-carbonium ion which partitions between enzyme to give the covalent galactosyl-enzyme and H2O to yield galactose.
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PMID:Oxygen-18 leaving group kinetic isotope effects on the hydrolysis of nitrophenyl glycosides. 1. beta-galactosidease-catalyzed hydrolysis. 678 82