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PDBsum entry 4lnn

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
4lnn
Jmol
Contents
Protein chains
(+ 6 more) 439 a.a.
Ligands
SO4 ×5
Metals
_MG ×25
Waters ×253
PDB id:
4lnn
Name: Ligase
Title: B. Subtilis glutamine synthetase structures reveal large act conformational changes and basis for isoenzyme specific reg structure of apo form of gs
Structure: Glutamine synthetase. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Synonym: glutamate--ammonia ligase. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Gene: glna, bsu17460. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
3.10Å     R-factor:   0.217     R-free:   0.267
Authors: M.A.Schumacher,N.Chinnam,N.Tonthat,S.Fisher,L.Wray
Key ref: D.S.Murray et al. (2013). Structures of the Bacillus subtilis glutamine synthetase dodecamer reveal large intersubunit catalytic conformational changes linked to a unique feedback inhibition mechanism. J Biol Chem, 288, 35801-35811. PubMed id: 24158439 DOI: 10.1074/jbc.M113.519496
Date:
11-Jul-13     Release date:   13-Nov-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P12425  (GLNA_BACSU) -  Glutamine synthetase
Seq:
Struc:
444 a.a.
439 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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
+ 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     6 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M113.519496 J Biol Chem 288:35801-35811 (2013)
PubMed id: 24158439  
 
 
Structures of the Bacillus subtilis glutamine synthetase dodecamer reveal large intersubunit catalytic conformational changes linked to a unique feedback inhibition mechanism.
D.S.Murray, N.Chinnam, N.K.Tonthat, T.Whitfill, L.V.Wray, S.H.Fisher, M.A.Schumacher.
 
  ABSTRACT  
 
Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in nitrogen metabolism. There are two main bacterial GS isoenzymes, GSI-α and GSI-β. GSI-α enzymes, which have not been structurally characterized, are uniquely feedback-inhibited by Gln. To gain insight into GSI-α function, we performed biochemical and cellular studies and obtained structures for all GSI-α catalytic and regulatory states. GSI-α forms a massive 600-kDa dodecameric machine. Unlike other characterized GS, the Bacillus subtilis enzyme undergoes dramatic intersubunit conformational alterations during formation of the transition state. Remarkably, these changes are required for active site construction. Feedback inhibition arises from a hydrogen bond network between Gln, the catalytic glutamate, and the GSI-α-specific residue, Arg(62), from an adjacent subunit. Notably, Arg(62) must be ejected for proper active site reorganization. Consistent with these findings, an R62A mutation abrogates Gln feedback inhibition but does not affect catalysis. Thus, these data reveal a heretofore unseen restructuring of an enzyme active site that is coupled with an isoenzyme-specific regulatory mechanism. This GSI-α-specific regulatory network could be exploited for inhibitor design against Gram-positive pathogens.