Disease relevance of glyA

• Characterization of the MetR binding sites for the glyA gene of Escherichia coli [1].
• To verify that the MetR binding sites play a functional role in glyA expression, site-directed mutagenesis was used to alter the two binding sites in a lambda glyA-lacZ gene fusion phage [1].

High impact information on glyA

• Escherichia coli serine hydroxymethyltransferase. The role of histidine 228 in determining reaction specificity [2].
• The results also showed that only one rotamer of 5-formyltetrahydrofolate binds at the active site of serine hydroxymethyltransferase [3].
• 5-Formyltetrahydrofolate polyglutamates are slow tight binding inhibitors of serine hydroxymethyltransferase [3].
• The interaction of the mono- and triglutamate forms of 5-methyltetrahydrofolate and 5-formyltetrahydrofolate with serine hydroxymethyltransferase were determined by several methods [3].
• Serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate [4].

Chemical compound and disease context of glyA

• Both rabbit liver mitochondrial and Escherichia coli serine hydroxymethyltransferase catalyze the conversion of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate at rates similar to those observed for the cytosolic enzyme [4].
• Role of methionine in the regulation of the synthesis of serine hydroxymethyltransferase in Escherichia coli [5].
• For Escherichia coli serine hydroxymethyltransferase each of these threonine residues has been changed to an alanine residue [6].
• A similar unfolding pathway has been reported for Escherichia coli aspartate aminotransferase, a member of the type I fold family of PLP binding enzymes such as SHMT, the sequence of which is only slightly identical ( approximately 14%) with that of SHMT [7].

Biological context of glyA

• The amino acid sequence of the amino and carboxy-terminal ends and the amino acid composition of cysteine-containing tryptic peptides were in agreement with the primary structure proposed for this enzyme from the structure of the glyA gene (M. Plamann, L. Stauffer, M. Urbanowski, and G. Stauffer, Nucleic Acids Res. 11:2065-2074, 1983) [8].
• Changing either binding site away from the consensus sequence caused a decrease in expression, suggesting that both sites are required for normal glyA regulation [1].
• The PurR binding site in the glyA promoter region of Escherichia coli [9].
• Serine hydroxymethyltransferase, in the presence of glycine, catalyzes the conversion of chemically synthesized 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate with biphasic kinetics [4].
• Serine hydroxymethyltransferase: origin of substrate specificity [6].

Associations of glyA with chemical compounds

• Homocysteine, a coregulator for MetR, increased MetR binding to the glyA control region [1].
• Hypoxanthine and guanine, co-repressors for PurR-mediated regulation of the pur regulon, increased binding of PurR to glyA operator DNA [9].
• Serine hydroxymethyltransferase has a conserved histidine residue (His-228) next to the lysine residue (Lys-229) which forms the internal aldimine with pyridoxal 5'-phosphate [2].
• This is consistent with homocysteine acting as an inducer and S-adenosylmethionine as a corepressor of serine hydroxymethyltransferase synthesis with high affinity for a repressor molecule [5].
• It is shown that serine hydroxymethyltransferase does not have absolute stereospecificity for the pro-2S-proton of glycine, but it catalyses the exchange of this proton 7400 times faster than the pro-2R proton of glycine [10].

Analytical, diagnostic and therapeutic context of glyA

• Sequence analysis of the glyA control region of Escherichia coli identified two regions with homology to the consensus binding sequence for MetR, a lysR family regulatory protein [1].

References