Disease relevance of glnA

• The top 10 homologs were all bacterial glutamine synthetases, including Salmonella typhimurium glnA [1].
• Cloned H. pylori glnA complemented a glnA mutation in E. coli, and GlnA enzyme activity could be measured spectrophotometrically [1].
• Role of glnA-linked genes in regulation of glutamine synthetase and histidase formation in Klebsiella aerogenes [2].
• To study ntrC transcription we have constructed operon fusions of ntrC to lacZ using the Casadaban Mu d1 (Apr lac) phage so that we can measure beta-galactosidase activity as a reflection of ntrC transcription and we have introduced into fusion strains promoter constitutive mutations at glnA [glnAp(Con)] [3].
• In enteric bacteria products of nitrogen regulatory genes ntrA, ntrB and ntrC are known to regulate transcription both positively and negatively at glnA, the structural gene encoding glutamine synthetase [L-glutamate:ammonia-ligase (ADP-forming), EC 6.3.1.2] [4].

High impact information on glnA

• Our model, which places the active sites at the subunit interfaces, suggests a mechanism for the main functional role of glutamine synthetase: how the enzyme regulates the rate of synthesis of glutamine in response to covalent modification and feedback inhibition [5].
• In the presence of adenosine triphosphate, the NtrC protein catalyzes isomerization of closed recognition complexes between sigma 54-holoenzyme and the glnA promoter to open complexes in which DNA in the region of the transcription start site is locally denatured [6].
• It bound to two different sites within the regulatory region of glnA (glutamine synthetase) and to one site in the regulatory region for the ntrBC operon [7].
• Enteric bacteria synthesize glutamate by the combined action of glutamine synthetase and glutamate synthase (GS/GOGAT cycle) or the action of biosynthetic glutamate dehydrogenase (GDH) [8].
• Bacterial glutamine synthetase (GS; EC 6.3.1.2) was previously shown to be inhibited by nine end products of glutamine metabolism [9].

Chemical compound and disease context of glnA

• Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine [9].
• L-Methionine SR-sulfoximine-resistant glutamine synthetase from mutants of Salmonella typhimurium [10].
• The resolution of the native structure of GS from Salmonella typhimurium has been extended to 2.5 A resolution, and the improved model is used to determine the structure of phosphinothricin complexed to GS by difference Fourier methods [11].
• The crystal structure of glutamine synthetase (GS) from Mycobacterium tuberculosis determined at 2.4 A resolution reveals citrate and AMP bound in the active site [12].
• Nitrogen control in Salmonella typhimurium is not limited to glutamine synthetase but affects, in addition, transport systems for histidine, glutamine, lysine-arginine-ornithine, and glutamate-aspartate [13].

Biological context of glnA

• This mutant strain, Peru2DeltaglnA, is unable to grow on medium that does not contain glutamine; this growth deficiency is complemented by pKEK71-NotI, a plasmid containing a complete copy of the Salmonella typhimurium glnA gene, or by pTIC5, a derivative of pKEK71-NotI containing a 1 [14].
• The glnA, ntrB, and ntrC genes form an operon [15].
• DNA sequencing of these four genes, manB, pduF, glnA, and spaM, showed no genetic diversity among the isolates tested, with a 100% identity in nucleotide sequence [16].
• The N-regulatory mutations are closely linked on the chromosome to the structural gene for glutamine synthetase, glnA: we discuss the possibility that they lie in a regulatory gene, glnR, which is distinct from glnA [13].
• Although this phenotype resembles that of mutants with lesions in the regulatory gene for glutamine synthetase, glnG, these mutations do not lie in the glnG gene [10].

Associations of glnA with chemical compounds

• In an attempt to produce a GlnA-deficient mutant of H. pylori, a kanamycin resistance cassette was cloned into the Tth111I site of H. pylori glnA [1].
• Studies of the S. typhimurium gdh strain in ammonia-limited continuous culture and of gdh glnA double-mutant strains indicated that decreases in the glutamine pool remained profound in strains with a single pathway for ammonia assimilation [17].
• Purification and characterization of the glutamine synthetase from one of the mutants and a control strain demonstrated that the mutant enzyme is defective in the reverse gamma-glutamyltransferase activity but has biosynthetic activity that is resistant to inhibition by L-methionine SR-sulfoximine [10].
• We provide evidence that ammonium, nitrate, and light regulate GS transcript accumulation in green algae [18].
• Analysis of GS transcript levels in mutants with defects in the nitrate assimilation pathway show that nitrate assimilation and ammonium assimilation are regulated independently [18].

Regulatory relationships of glnA

• Missense mutations in glutamine synthetase that constitutively express the TnrA-regulated amtB gene were characterized [19].

Other interactions of glnA

• For the MLST analysis, the manB, pduF, glnA, and spaM genes were amplified by PCR from the same 85 isolates [16].
• The regulation of glutamate dehydrogenase (EC 1.4.1.4), glutamine synthetase (EC 6.3.1.2), and glutamate synthase (EC 2.6.1.53) was examined for cultures of Salmonella typhimurium grown with various nitrogen and amino acid sources [20].
• Furthermore, all of the phosphotyrosine detectable in partial acid hydrolysates of 32P-labeled Salmonella typhimurium was eliminated in a strain deficient in both glutamine synthetase and uridylyltransferase, an enzyme which uridylylates the regulatory protein PII at a tyrosine residue [21].

Analytical, diagnostic and therapeutic context of glnA

• We present an atomic model for glutamine synthetase, an enzyme of central importance in bacterial nitrogen metabolism, from X-ray crystallography [5].
• The molecular mechanism for this metal-induced self-assembly of the E. coli GS has been studied by molecular modeling and site-directed mutagenesis [22].
• Isolation and crystallization of unadenylylated glutamine synthetase from Salmonella typhimurium [23].

References