spacer
spacer

PDBsum entry 2lgs

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Ligase(amide synthetase) PDB id
2lgs
Jmol
Contents
Protein chains
(+ 6 more) 445 a.a. *
Ligands
GLU ×12
Metals
_MN ×24
* Residue conservation analysis
PDB id:
2lgs
Name: Ligase(amide synthetase)
Title: Feedback inhibition of fully unadenylylated glutamine synthetase from salmonella typhimurium by glycine, alanine, and serine
Structure: Glutamine synthetase. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Engineered: yes
Source: Salmonella typhimurium. Organism_taxid: 602
Biol. unit: Dodecamer (from PQS)
Resolution:
2.80Å     R-factor:   0.235    
Authors: S.-H.Liaw,D.Eisenberg
Key ref: S.H.Liaw et al. (1993). Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine. Proc Natl Acad Sci U S A, 90, 4996-5000. PubMed id: 8099447 DOI: 10.1073/pnas.90.11.4996
Date:
05-Aug-94     Release date:   30-Nov-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A1P6  (GLNA_SALTY) -  Glutamine synthetase
Seq:
Struc:
469 a.a.
445 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.6.3.1.2  - Glutamate--ammonia ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine
ATP
+
L-glutamate
Bound ligand (Het Group name = GLU)
corresponds exactly
+ NH(3)
= ADP
+ phosphate
+ L-glutamine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     nitrogen compound metabolic process   3 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.90.11.4996 Proc Natl Acad Sci U S A 90:4996-5000 (1993)
PubMed id: 8099447  
 
 
Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine.
S.H.Liaw, C.Pan, D.Eisenberg.
 
  ABSTRACT  
 
Bacterial glutamine synthetase (GS; EC 6.3.1.2) was previously shown to be inhibited by nine end products of glutamine metabolism. Here we present four crystal structures of GS, complexed with the substrate Glu and with each of three feedback inhibitors. The GS of the present study is from Salmonella typhimurium, with Mn2+ ions bound, and is fully unadenylylated. From Fourier difference maps, we find that L-serine, L-alanine, and glycine bind at the site of the substrate L-glutamate. In our model, these four amino acids bind with the atoms they share in common (the "main chain" +NH3-CH-COO-) in the same positions. Thus on the basis of our x-ray work, glycine, alanine, and serine appear to inhibit GS-Mn by competing with the substrate glutamate for the active site.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21481771 J.M.van Rooyen, V.R.Abratt, H.Belrhali, and T.Sewell (2011).
Crystal structure of Type III glutamine synthetase: surprising reversal of the inter-ring interface.
  Structure, 19, 471-483.
PDB code: 3o6x
20656908 L.V.Wray, and S.H.Fisher (2010).
Functional roles of the conserved Glu304 loop of Bacillus subtilis glutamine synthetase.
  J Bacteriol, 192, 5018-5025.  
19322816 Y.X.He, L.Gui, Y.Z.Liu, Y.Du, Y.Zhou, P.Li, and C.Z.Zhou (2009).
Crystal structure of Saccharomyces cerevisiae glutamine synthetase Gln1 suggests a nanotube-like supramolecular assembly.
  Proteins, 76, 249-254.
PDB code: 3fky
16460515 J.L.Ortega, S.Moguel-Esponda, C.Potenza, C.F.Conklin, A.Quintana, and C.Sengupta-Gopalan (2006).
The 3' untranslated region of a soybean cytosolic glutamine synthetase (GS1) affects transcript stability and protein accumulation in transgenic alfalfa.
  Plant J, 45, 832-846.  
16041744 J.Hiratake (2005).
Enzyme inhibitors as chemical tools to study enzyme catalysis: rational design, synthesis, and applications.
  Chem Rec, 5, 209-228.  
16027359 W.W.Krajewski, T.A.Jones, and S.L.Mowbray (2005).
Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights.
  Proc Natl Acad Sci U S A, 102, 10499-10504.
PDB code: 2bvc
12957965 A.Van Dommelen, V.Keijers, A.Wollebrants, and J.Vanderleyden (2003).
Phenotypic changes resulting from distinct point mutations in the Azospirillum brasilense glnA gene, encoding glutamine synthetase.
  Appl Environ Microbiol, 69, 5699-5701.  
12730324 L.Reitzer (2003).
Nitrogen assimilation and global regulation in Escherichia coli.
  Annu Rev Microbiol, 57, 155-176.  
12824490 M.I.Muro-Pastor, F.N.Barrera, J.C.Reyes, F.J.Florencio, and J.L.Neira (2003).
The inactivating factor of glutamine synthetase, IF7, is a "natively unfolded" protein.
  Protein Sci, 12, 1443-1454.  
12139611 S.H.Fisher, J.L.Brandenburg, and L.V.Wray (2002).
Mutations in Bacillus subtilis glutamine synthetase that block its interaction with transcription factor TnrA.
  Mol Microbiol, 45, 627-635.  
11329256 H.S.Gill, and D.Eisenberg (2001).
The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition.
  Biochemistry, 40, 1903-1912.
PDB codes: 1f1h 1f52 1fpy
10224282 G.Harth, and M.A.Horwitz (1999).
An inhibitor of exported Mycobacterium tuberculosis glutamine synthetase selectively blocks the growth of pathogenic mycobacteria in axenic culture and in human monocytes: extracellular proteins as potential novel drug targets.
  J Exp Med, 189, 1425-1436.  
10583418 J.L.Crespo, M.G.Guerrero, and F.J.Florencio (1999).
Mutational analysis of Asp51 of Anabaena azollae glutamine synthetase. D51E mutation confers resistance to the active site inhibitors L-methionine-DL-sulfoximine and phosphinothricin.
  Eur J Biochem, 266, 1202-1209.  
9737857 P.Jiang, J.A.Peliska, and A.J.Ninfa (1998).
The regulation of Escherichia coli glutamine synthetase revisited: role of 2-ketoglutarate in the regulation of glutamine synthetase adenylylation state.
  Biochemistry, 37, 12802-12810.  
  9209053 P.Jiang, P.Zucker, M.R.Atkinson, E.S.Kamberov, W.Tirasophon, P.Chandran, B.R.Schefke, and A.J.Ninfa (1997).
Structure/function analysis of the PII signal transduction protein of Escherichia coli: genetic separation of interactions with protein receptors.
  J Bacteriol, 179, 4342-4353.  
  8563633 S.H.Liaw, I.Kuo, and D.Eisenberg (1995).
Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site.
  Protein Sci, 4, 2358-2365.  
  7913929 R.B.Helling (1994).
Why does Escherichia coli have two primary pathways for synthesis of glutamate?
  J Bacteriol, 176, 4664-4668.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.