PDBsum entry 1hto

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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
Protein chains
(+ 18 more) 477 a.a. *
AMP ×24
CIT ×24
_MN ×24
Waters ×6312
* Residue conservation analysis
PDB id:
Name: Ligase
Title: Crystallographic structure of a relaxed glutamine synthetase mycobacterium tuberculosis
Structure: Glutamine synthetase. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p, q, r v, w, x. Synonym: gs, glutamate--ammonia ligase 1. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dodecamer (from PQS)
2.40Å     R-factor:   0.227     R-free:   0.255
Authors: H.S.Gill,D.Eisenberg,Tb Structural Genomics Consortium (Tbsg
Key ref:
H.S.Gill et al. (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. PubMed id: 12146952 DOI: 10.1021/bi020254s
01-Jan-01     Release date:   24-Jul-02    
Go to PROCHECK summary

Protein chains
P9WN39  (GLNA1_MYCTU) -  Glutamine synthetase 1
478 a.a.
477 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
Bound ligand (Het Group name = CIT)
matches with 64.29% similarity
+ NH(3)
Bound ligand (Het Group name = AMP)
matches with 85.19% similarity
+ 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: 10.1021/bi020254s Biochemistry 41:9863-9872 (2002)
PubMed id: 12146952  
Multicopy crystallographic refinement of a relaxed glutamine synthetase from Mycobacterium tuberculosis highlights flexible loops in the enzymatic mechanism and its regulation.
H.S.Gill, G.M.Pfluegl, D.Eisenberg.
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. The structure was refined with strict 24-fold noncrystallographic symmetry (NCS) constraints and has an R-factor of 22.7% and an R-free of 25.5%. Multicopy refinement using 10 atomic models and strict 24-fold NCS constraints further reduced the R-factor to 20.4% and the R-free to 23.2%. The multicopy model demonstrates the range of atomic displacements of catalytic and regulatory loops in glutamine synthesis, simulating loop motions. A comparison with loop positions in substrate complexes of GS from Salmonella typhimurium shows that the Asp50 and Glu327 loops close over the active site during catalysis. These loop closures are preceded by a conformational change of the Glu209 beta-strand upon metal ion or ATP binding that converts the enzyme from a relaxed to a taut state. We propose a model of the GS regulatory mechanism based on the loop motions in which adenylylation of the Tyr397 loop reverses the effect of metal ion binding, and regulates intermediate formation by preventing closure of the Glu327 loop.

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
21036868 P.W.Rose, B.Beran, C.Bi, W.F.Bluhm, D.Dimitropoulos, D.S.Goodsell, A.Prlic, M.Quesada, G.B.Quinn, J.D.Westbrook, J.Young, B.Yukich, C.Zardecki, H.M.Berman, and P.E.Bourne (2011).
The RCSB Protein Data Bank: redesigned web site and web services.
  Nucleic Acids Res, 39, D392-D401.  
20071215 C.A.Broberg, and K.Orth (2010).
Tipping the balance by manipulating post-translational modifications.
  Curr Opin Microbiol, 13, 34-40.  
20823548 E.Pozharski (2010).
Percentile-based spread: a more accurate way to compare crystallographic models.
  Acta Crystallogr D Biol Crystallogr, 66, 970-978.  
18992257 N.Narayana, and M.A.Weiss (2009).
Crystallographic analysis of a sex-specific enhancer element: sequence-dependent DNA structure, hydration, and dynamics.
  J Mol Biol, 385, 469-490.
PDB code: 3bse
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.  
18469098 P.Carroll, C.A.Pashley, and T.Parish (2008).
Functional analysis of GlnE, an essential adenylyl transferase in Mycobacterium tuberculosis.
  J Bacteriol, 190, 4894-4902.  
17850744 E.J.Levin, D.A.Kondrashov, G.E.Wesenberg, and G.N.Phillips (2007).
Ensemble refinement of protein crystal structures: validation and application.
  Structure, 15, 1040-1052.
PDB codes: 2q3m 2q3o 2q3p 2q3q 2q3r 2q3s 2q3t 2q3u 2q3v 2q3w 2q40 2q41 2q42 2q43 2q44 2q45 2q46 2q47 2q48 2q49 2q4a 2q4b 2q4c 2q4d 2q4e 2q4f 2q4h 2q4i 2q4j 2q4k 2q4l 2q4m 2q4n 2q4o 2q4p 2q4q 2q4r 2q4s 2q4t 2q4u 2q4v 2q4x 2q4y 2q4z 2q50 2q51 2q52
17178129 J.G.McCoy, E.Bitto, C.A.Bingman, G.E.Wesenberg, R.M.Bannen, D.A.Kondrashov, and G.N.Phillips (2007).
Structure and dynamics of UDP-glucose pyrophosphorylase from Arabidopsis thaliana with bound UDP-glucose and UTP.
  J Mol Biol, 366, 830-841.
PDB codes: 1z90 2icx 2icy
17242521 M.Novotny, M.Seibert, and G.J.Kleywegt (2007).
On the precision of calculated solvent-accessible surface areas.
  Acta Crystallogr D Biol Crystallogr, 63, 270-274.  
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
16262797 G.Harth, S.Maslesa-Galić, M.V.Tullius, and M.A.Horwitz (2005).
All four Mycobacterium tuberculosis glnA genes encode glutamine synthetase activities but only GlnA1 is abundantly expressed and essential for bacterial homeostasis.
  Mol Microbiol, 58, 1157-1172.  
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
15662999 H.Park, and S.Lee (2004).
Homology modeling, force field design, and free energy simulation studies to optimize the activities of histone deacetylase inhibitors.
  J Comput Aided Mol Des, 18, 375-388.  
15037612 R.Mehta, J.T.Pearson, S.Mahajan, A.Nath, M.J.Hickey, D.R.Sherman, and W.M.Atkins (2004).
Adenylylation and catalytic properties of Mycobacterium tuberculosis glutamine synthetase expressed in Escherichia coli versus mycobacteria.
  J Biol Chem, 279, 22477-22482.  
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
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.