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PDBsum entry 1f1h

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
1f1h
Jmol
Contents
Protein chains
(+ 6 more) 468 a.a. *
Ligands
ADP ×12
MPD ×12
Metals
_MN ×24
_TL ×24
Waters ×1452
* Residue conservation analysis
PDB id:
1f1h
Name: Ligase
Title: Crystal structure of glutamine synthetase from salmonella typhimurium with thallium ions
Structure: Protein (glutamine synthetase). Chain: a, b, c, d, e, f, g, h, i, j, k, l. Ec: 6.3.1.2
Source: Salmonella typhimurium. Organism_taxid: 602. Other_details: gram negative bacteria
Biol. unit: Dodecamer (from PQS)
Resolution:
2.67Å     R-factor:   0.232     R-free:   0.263
Authors: H.S.Gill,D.Eisenberg
Key ref:
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. PubMed id: 11329256 DOI: 10.1021/bi002438h
Date:
19-May-00     Release date:   04-Apr-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A1P6  (GLNA_SALTY) -  Glutamine synthetase
Seq:
Struc:
469 a.a.
468 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
+ NH(3)
=
ADP
Bound ligand (Het Group name = ADP)
corresponds exactly
+ 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: 10.1021/bi002438h Biochemistry 40:1903-1912 (2001)
PubMed id: 11329256  
 
 
The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition.
H.S.Gill, D.Eisenberg.
 
  ABSTRACT  
 
Phosphinothricin is a potent inhibitor of the enzyme glutamine synthetase (GS). 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. The structure suggests a noncovalent, dead-end mechanism of inhibition. Phosphinothricin occupies the glutamate substrate pocket and stabilizes the Glu327 flap in a position which blocks the glutamate entrance to the active site, trapping the inhibitor on the enzyme. One oxygen of the phosphinyl group of phosphinothricin appears to be protonated, because of its proximity to the carboxylate group of Glu327. The other phosphinyl oxygen protrudes into the negatively charged binding pocket for the substrate ammonium, disrupting that pocket. The distribution of charges in the glutamate binding pocket is complementary to those of phosphinothricin. The presence of a second ammonium binding site within the active site is confirmed by its analogue thallous ion, marking the ammonium site and its protein ligands. The inhibition of GS by methionine sulfoximine can be explained by the same mechanism. These models of inhibited GS further illuminate its catalytic mechanism.
 

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
20839295 C.J.Illingworth, P.D.Scott, K.E.Parkes, C.R.Snell, M.P.Campbell, and C.A.Reynolds (2010).
Connectivity and binding-site recognition: applications relevant to drug design.
  J Comput Chem, 31, 2677-2688.  
19233925 S.H.Fisher, and L.V.Wray (2009).
Novel trans-Acting Bacillus subtilis glnA mutations that derepress glnRA expression.
  J Bacteriol, 191, 2485-2492.  
19596908 W.B.Inwood, J.A.Hall, K.S.Kim, L.Demirkhanyan, D.Wemmer, H.Zgurskaya, and S.Kustu (2009).
Epistatic effects of the protease/chaperone HflB on some damaged forms of the Escherichia coli ammonium channel AmtB.
  Genetics, 183, 1327-1340.  
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
18074244 N.K.Rana, P.Mohanpuria, and S.K.Yadav (2008).
Cloning and characterization of a cytosolic glutamine synthetase from Camellia sinensis (L.) O. Kuntze that is upregulated by ABA, SA, and H2O2.
  Mol Biotechnol, 39, 49-56.  
17991033 J.Jones, D.J.Studholme, C.G.Knight, and G.M.Preston (2007).
Integrated bioinformatic and phenotypic analysis of RpoN-dependent traits in the plant growth-promoting bacterium Pseudomonas fluorescens SBW25.
  Environ Microbiol, 9, 3046-3064.  
17112226 B.Gold, L.M.Marky, M.P.Stone, and L.D.Williams (2006).
A review of the role of the sequence-dependent electrostatic landscape in DNA alkylation patterns.
  Chem Res Toxicol, 19, 1402-1414.  
17161372 K.Wyatt, H.E.White, L.Wang, O.A.Bateman, C.Slingsby, E.V.Orlova, and G.Wistow (2006).
Lengsin is a survivor of an ancient family of class I glutamine synthetases re-engineered by evolution for a role in the vertebrate lens.
  Structure, 14, 1823-1834.
PDB code: 2j9i
16885465 S.H.Fisher, and L.V.Wray (2006).
Feedback-resistant mutations in Bacillus subtilis glutamine synthetase are clustered in the active site.
  J Bacteriol, 188, 5966-5974.
PDB code: 2fwx
16161106 A.M.Davies, R.Tata, R.Agha, B.J.Sutton, and P.R.Brown (2005).
Crystal structure of a putative phosphinothricin acetyltransferase (PA4866) from Pseudomonas aeruginosa PAC1.
  Proteins, 61, 677-679.
PDB code: 2bl1
16055443 L.V.Wray, and S.H.Fisher (2005).
A feedback-resistant mutant of Bacillus subtilis glutamine synthetase with pleiotropic defects in nitrogen-regulated gene expression.
  J Biol Chem, 280, 33298-33304.  
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
15211520 C.Lehmann, V.Doseeva, S.Pullalarevu, W.Krajewski, A.Howard, and O.Herzberg (2004).
YbdK is a carboxylate-amine ligase with a gamma-glutamyl:Cysteine ligase activity: crystal structure and enzymatic assays.
  Proteins, 56, 376-383.
PDB code: 1r8g
14500881 K.Matsuda, T.Nishioka, K.Kinoshita, T.Kawabata, and N.Go (2003).
Finding evolutionary relations beyond superfamilies: fold-based superfamilies.
  Protein Sci, 12, 2239-2251.  
12717724 S.B.Howerton, A.Nagpal, and L.D.Williams (2003).
Surprising roles of electrostatic interactions in DNA-ligand complexes.
  Biopolymers, 69, 87-99.
PDB code: 1p20
12717031 S.Wang, and D.Eisenberg (2003).
Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate.
  Protein Sci, 12, 1097-1108.
PDB codes: 1mop 1n2b 1n2e 1n2g 1n2h 1n2i 1n2j 1n2o
12146952 H.S.Gill, G.M.Pfluegl, and D.Eisenberg (2002).
Multicopy crystallographic refinement of a relaxed glutamine synthetase from Mycobacterium tuberculosis highlights flexible loops in the enzymatic mechanism and its regulation.
  Biochemistry, 41, 9863-9872.
PDB codes: 1hto 1htq
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.  
11553771 K.Motohashi, A.Kondoh, M.T.Stumpp, and T.Hisabori (2001).
Comprehensive survey of proteins targeted by chloroplast thioredoxin.
  Proc Natl Acad Sci U S A, 98, 11224-11229.  
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.