Disease relevance of metE

• In Salmonella typhimurium the metE and metR promoters overlap and are divergently transcribed [1].
• Regulation of methionine synthesis in Escherichia coli: effect of the MetR protein on the expression of the metE and metR genes [2].

High impact information on metE

• In addition, truncation studies have identified a region on MetR that may be involved in the homocysteine activation of metE expression [3].
• A plasmid (pRSE562) containing the metE and metR genes of Escherichia coli was used to study the expression of these genes and the role of the MetR protein in regulating metE expression [2].
• When this plasmid was used to transform either wild-type E. coli, metE mutant, or metR mutant, MetE enzyme activity increased 5- to 7-fold over wild-type levels [2].
• We have determined the nucleotide sequence for the metE gene, encoding the cobalamin-independent methionine synthase [4].
• Upstream of yagD and overlapping with its reading frame is a gene (ykfD) which, when inactivated, also blocks growth on methylmethionine in a metE metH genetic background [5].

Chemical compound and disease context of metE

• Transcription of the metE gene in Salmonella typhimurium and Escherichia coli is positively regulated by the MetR protein, with homocysteine serving as a coactivator [6].

Biological context of metE

• Three tandem repeats of an 8 bp sequence defined previously as the metE operator site for MetJ-mediated repression also overlap the -35 region of the metR promoter [1].
• In this study, we show that purified MetR protein also binds to and protects a second 24-bp sequence adjacent to the original site, from nucleotides -24 to -47 relative to the metE transcription initiation site (designated as site 2) [6].
• Characterization of a second MetR-binding site in the metE metR regulatory region of Salmonella typhimurium [6].
• Base pair changes in site 1 or site 2 away from the MetR consensus binding sequence resulted in decreased metE-lacZ expression, suggesting that both sites are necessary for expression [6].
• Via its N-terminal amino acid sequence, the 34-kDa polypeptide was identified as the metE gene product [7].

Associations of metE with chemical compounds

• The altered regulation of these genes occurs in the presence of high intracellular levels of homocysteine, a methionine pathway intermediate which normally inhibits metH and metR expression and stimulates metE expression [8].
• The latter two classes of mutations also affected regulation of the metE gene of the folate branch of the methionine pathway, but not metA in the nonfolate branch of the methionine pathway, or the gcv operon, encoding the glycine cleavage enzyme system [9].

Other interactions of metE

• The DNA-binding protein MetR belongs to the LysR family of transcriptional activators and is required for expression of the metE and metH promoters in Escherichia coli [10].
• Single and multiple base changes were introduced into sites 1 and 2 in a metE-lacZ fusion [6].

References