Disease relevance of ECs4931

• HTS is the first biosynthetic E. coli enzyme shown to have a short half-life and may represent a group of biosynthetic enzymes whose expression is controlled by proteolysis [1].

High impact information on ECs4931

• Homoserine trans-succinylase (HTS), the first enzyme in the methionine biosynthetic pathway, aggregates at temperatures higher than 44 degrees C in vitro [2].
• The elevated level of HTS was a result of transcriptional activation of the metA gene [3].
• In order to determine the relationship between this control mechanism and the heat shock response, we estimated the cellular levels of HTS during heat shock by Western (immunoblot) analysis and found an increase following induction by temperature shift and by addition of ethanol or cadmium ions [3].
• These results suggest a metabolic link between the two systems that control the response of E. coli to elevated temperatures: the metA gene, which codes for the enzyme responsible for regulating cell growth as a function of temperature elevation (HTS), is transcriptionally activated by the heat shock response [3].
• In P. fluorescens metA Rifr mutants carrying the F110 plasmid, which carried the E. coli metA gene and the E. coli rifs allele, sensitivity to rifampin was found to be dominant at least temporarily over resistance [4].

Chemical compound and disease context of ECs4931

• In Escherichia coli, the growth rate at elevated temperatures is controlled by the availability of endogenous methionine, which is limited because of the temperature sensitivity of the metA gene product, homoserine transsuccinylase (HTS) [3].

Biological context of ECs4931

• DNA replication proteins represent a class of extremely well-established anti-infective drug targets for which improvements in assay technology are required in order to support enzyme characterization, HTS, and structure-activity relationship studies [5].

Associations of ECs4931 with chemical compounds

• The results presented here indicate that the first enzyme in methionine biosynthesis - homoserine trans-succinylase (HTS) - is unstable and subject to energy-dependent proteolysis [1].

Analytical, diagnostic and therapeutic context of ECs4931

• Titration NMR experiments with the selected reference compound are performed for finding the optimal set-up conditions for HTS and for deriving the binding constants of the identified NMR hits [6].

References