PDBsum entry 2bvc

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
Protein chains
(+ 0 more) 475 a.a. *
P3S ×6
ADP ×6
_CL ×6
_MG ×18
Waters ×621
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystal structure of mycobacterium tuberculosis glutamine synthetase in complex with a transition state mimic
Structure: Glutamine synthetase 1. Chain: a, b, c, d, e, f. Synonym: glutamate ammonia ligase 1. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Dodecamer (from PDB file)
2.1Å     R-factor:   0.193     R-free:   0.230
Authors: W.W.Krajewski,T.A.Jones,S.L.Mowbray
Key ref:
W.W.Krajewski et al. (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. PubMed id: 16027359 DOI: 10.1073/pnas.0502248102
23-Jun-05     Release date:   07-Jul-05    
Go to PROCHECK summary

Protein chains
P9WN39  (GLNA1_MYCTU) -  Glutamine synthetase 1
478 a.a.
475 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glutamate--ammonia ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine
+ L-glutamate
+ NH(3)
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     extracellular region   5 terms 
  Biological process     growth   4 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1073/pnas.0502248102 Proc Natl Acad Sci U S A 102:10499-10504 (2005)
PubMed id: 16027359  
Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights.
W.W.Krajewski, T.A.Jones, S.L.Mowbray.
Glutamine synthetase catalyzes the ligation of glutamate and ammonia to form glutamine, with the resulting hydrolysis of ATP. The enzyme is a central component of bacterial nitrogen metabolism and is a potential drug target. Here, we report a high-yield recombinant expression system for glutamine synthetase of Mycobacterium tuberculosis together with a simple purification. The procedure allowed the structure of a complex with a phosphorylated form of the inhibitor methionine sulfoximine, magnesium, and ADP to be solved by molecular replacement and refined at 2.1-A resolution. To our knowledge, this study provides the first reported structure for a taut form of the M. tuberculosis enzyme, similar to that observed for the Salmonella enzyme earlier. The phospho compound, generated in situ by an active enzyme, mimics the phosphorylated tetrahedral adduct at the transition state. Some differences in ligand interactions of the protein with both phosphorylated compound and nucleotide are observed compared with earlier structures; a third metal ion also is found. The importance of these differences in the catalytic mechanism is discussed; the results will help guide the search for specific inhibitors of potential therapeutic interest.
  Selected figure(s)  
Figure 1.
Fig. 1. Overall MtGS structure. (A) The subunits of the MtGS hexamer are colored either gold/red or green/blue. Ball-and-stick representations of MSO-P and ADP (black) show the location of the active sites at subunit-subunit interfaces. (B) The -strand register shift that distinguishes the current taut structure of MtGS (gold carbons) from the previous relaxed one (dark gray carbons) is shown. Residues of the relaxed structure are underlined.
Figure 3.
Fig. 3. Comparisons of MtGS with YbdK and -GCS. (A) The C backbones of the complex form of -GCS (blue) and the apo form of the YbdK protein (red) were superimposed on that of the A molecule of MtGS/MSO-P/MgADP (green) by using the superposition described in Table 2. For -GCS and MtGS, ADP and phosphorylated inhibitor are shown. (B) The active sites of MtGS (gold carbons) and -GCS (steel-gray carbons) are compared. Metal ions of the two structures are shown in magenta and blue, respectively. Interacting residues of MtGS are labeled.
  Figures were selected by an automated process.  

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.  
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.  
19422547 S.M.Bernard, and D.Z.Habash (2009).
The importance of cytosolic glutamine synthetase in nitrogen assimilation and recycling.
  New Phytol, 182, 608-620.  
19148777 Y.Li, G.Yang, X.Huang, B.Ye, M.Liu, Z.Lin, C.Li, and Z.A.Cao (2009).
Recombinant glutamine synthetase (GS) from C. glutamicum existed as both hexamers & dedocamers and C-terminal His-tag enhanced inclusion bodies formation in E. coli.
  Appl Biochem Biotechnol, 159, 614-622.  
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
17154526 M.Morar, R.Anand, A.A.Hoskins, J.Stubbe, and S.E.Ealick (2006).
Complexed structures of formylglycinamide ribonucleotide amidotransferase from Thermotoga maritima describe a novel ATP binding protein superfamily.
  Biochemistry, 45, 14880-14895.
PDB codes: 2hru 2hry 2hs0 2hs3 2hs4
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
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.