Disease relevance of glyA

• A novel mechanism for upregulation of the Escherichia coli K-12 hmp (flavohaemoglobin) gene by the 'NO releaser', S-nitrosoglutathione: nitrosation of homocysteine and modulation of MetR binding to the glyA-hmp intergenic region [1].
• Identification of glyA as a symbiotically essential gene in Bradyrhizobium japonicum [2].
• Cloning and expression of the Campylobacter jejuni glyA gene in Escherichia coli [3].
• A plasmid containing the glyA gene of Salmonella typhimurium LT2 was constructed in vitro using plasmid pACYC184 as the cloning vector and a lambda gt7-glyA transducing phage as the source of glyA DNA [4].
• The glyA gene encoding a serine hydroxymethyl transferase (SHMT) with threonine aldolase activity was isolated from Streptococcus thermophilus YKA-184 chromosomal DNA [5].

High impact information on glyA

• From the genome analysis of the Mycobacterium tuberculosis two putative genes namely GlyA and GlyA2 have been proposed to encode for the enzyme serine hydroxymethyltransferase [6].
• The results are discussed in terms of the role of each Pro residue in maintaining the structure and function of SHMT and a possible role in pyridoxal 5'-phosphate addition to the apo-enzyme [7].
• Role of proline residues in the folding of serine hydroxymethyltransferase [7].
• The 5 Pro residues were each mutated to both a Gly and Ala residue, and each mutant SHMT was purified and characterized with respect to kinetic properties, stability, secondary structure, and folding mechanism [7].
• The first structure of the serine-bound form of SHMT allows identification of residues involved in serine binding and catalysis [8].

Chemical compound and disease context of glyA

• The methionine component of glyA gene regulation in Escherichia coli K-12 was investigated [9].
• The purine regulon repressor protein, PurR, was shown to be a purine component involved in glyA regulation in Escherichia coli [10].
• A constructed strain of E. coli, MD901 (glyA thrB/C tdh), was unable to grow unless both glycine and threonine were added to defined rich medium [11].
• The sequence of tryptic and chymotryptic peptides from cytosolic and mitochondrial rabbit liver serine hydroxymethyltransferase are compared to the proposed sequence of a protein coded for by the glyA gene of Escherichia coli [12].
• Crystal structure at 2.4 A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate [13].

Biological context of glyA

• We propose that the previously documented modulation by Hcy of MetR binding to the glyA-hmp intergenic regulatory region regulates hmp transcription [1].
• Previously, we demonstrated that expression of CsgD from a multicopy plasmid increased expression of the glyA gene, which codes for serine hydroxymethyltransferase [14].
• After the coding region there is a 185 nucleotide sequence preceding the proposed transcription termination region for the glyA gene [15].
• These stem-loop structures show remarkable homology with intercistronic elements of other prokaryotic operons and may play a role in the regulation of glyA gene expression [15].
• The gene ssyA was mapped at a new locus between hisS and glyA on the chromosome [16].

Anatomical context of glyA

• A comparison of the site of each Tn5 insertion within the glyA gene or within gene X and the size of the polypeptide observed in the cell-free system enabled us to determine the direction of transcription and translation of both genes [17].
• Serine hydroxymethyltransferase (SHMT) from plant mitochondria was shown to be inhibited by 5-CHO-H(4)PteGlu(n) as are SHMTs from other organisms [18].
• Serine hydroxymethyltransferase purified from rabbit liver cytosol has at least two Asn residues (Asn(5) and Asn(220)) that are 67 and 30% deamidated, respectively [19].

Associations of glyA with chemical compounds

• Activation of glyA by the MetR protein requires homocysteine, an intermediate in methionine biosynthesis [9].
• The increase in SHMT activity was sufficient to correct the glycine auxotrophy of strains lacking folA [20].
• The mutation responsible for these phenotypes mapped to the glyA gene, a biosynthetic gene encoding the enzyme that converts serine and tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate [21].
• The glyA gene was identified on the insert by analyzing a set of plasmids derived from pGS1 that carry random insertions of the transposable kanamycin resistance element Tn5 [22].
• The presence of hypoxanthine, the co-repressor of PurR, increases the ability of PurR to prevent RNAP binding, providing a model for repression of the glyA gene by PurR [23].

Other interactions of glyA

• Regulation of the Escherichia coli glyA gene by the purR gene product [10].
• Regulation of the Escherichia coli glyA gene by the metR gene product and homocysteine [9].
• Escherichia coli glyA mRNA decay: the role of 3' secondary structure and the effects of the pnp and rnb mutations [24].

Analytical, diagnostic and therapeutic context of glyA

• This DNA manipulation allowed us to perform site-directed mutagenesis by PCR on the glyA gene [25].
• Properties of a serine hydroxymethyltransferase in which an active site histidine has been changed to an asparagine by site-directed mutagenesis [26].
• Diffraction grade crystals of serine hydroxymethyltransferase were obtained after extensive screening of source of enzyme, purification procedures, ligand binding and crystallization conditions [27].
• However, development of resistance to drugs, due to a variety of reasons, has necessitated the identification of alternate targets for cancer chemotherapy and serine hydroxymethyltransferase is one such potential target [28].
• Purification of serine hydroxymethyltransferase from Bacillus stearothermophilus with ion-exchange high-performance liquid chromatography [29].

References