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Tglutamine amidotransferase PDB id
1ao0
Jmol
Contents
Protein chains
455 a.a. *
Ligands
SF4 ×4
5GP ×4
ADP ×4
Metals
_MG ×4
Waters ×4
* Residue conservation analysis
PDB id:
1ao0
Name: Tglutamine amidotransferase
Title: Glutamine phosphoribosylpyrophosphate (prpp) amidotransferase from b. Subtilis complexed with adp and gmp
Structure: Glutamine phosphoribosylpyrophosphate amidotransferase. Chain: a, b, c, d. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Gene: purf. Expressed in: escherichia coli. Expression_system_taxid: 562. Into puc18)
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
2.80Å     R-factor:   0.214     R-free:   0.264
Authors: D.R.Tomchick,J.L.Smith
Key ref:
S.Chen et al. (1997). Mechanism of the synergistic end-product regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides. Biochemistry, 36, 10718-10726. PubMed id: 9271502 DOI: 10.1021/bi9711893
Date:
15-Jul-97     Release date:   12-Nov-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00497  (PUR1_BACSU) -  Amidophosphoribosyltransferase
Seq:
Struc: 		476 a.a.
455 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.4.2.14  - Amidophosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 5-phospho-beta-D-ribosylamine + diphosphate + L-glutamate = L-glutamine + 5-phospho-alpha-D-ribose 1-diphosphate + H2O
5-phospho-beta-D-ribosylamine
Bound ligand (Het Group name = 5GP)
matches with 58.00% similarity 		+ diphosphate
 + L-glutamate
 = L-glutamine
 +
5-phospho-alpha-D-ribose 1-diphosphate
Bound ligand (Het Group name = ADP)
matches with 53.00% similarity 		+ H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   5 terms 
  Biochemical function     transferase activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi9711893 Biochemistry 36:10718-10726 (1997)
PubMed id: 9271502  
 
 
Mechanism of the synergistic end-product regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides.
S.Chen, D.R.Tomchick, D.Wolle, P.Hu, J.L.Smith, R.L.Switzer, H.Zalkin.
 
  ABSTRACT  
 
De novo purine nucleotide synthesis is regulated, at least in part, by end-product inhibition of glutamine PRPP amidotransferase. An important feature of this inhibition is the fact that certain synergistic nucleotide pairs give more than additive inhibition. The physiological importance of synergism is in amplifying regulation by the adenine and guanine nucleotide end products of de novo synthesis. Using a new method to quantitate synergism, ADP plus GMP were to give strong synergistic inhibition of Bacillus subtilis glutamine PRPP amidotransferase. An X-ray structure of the ternary enzyme.ADP.GMP complex established that ADP binds to the allosteric A site and GMP to the catalytic C site. GMP increased the binding affinity of ADP for the A site by approximately 20-fold. Synergism results from a specific nucleotide-nucleotide interaction that is dependent upon a nucleoside diphosphate in the A site and a nucleoside monophosphate in the C site. Furthermore, synergism is enhanced by the competition between nucleotide inhibitor and PRPP substrate for the C site. Purine base specificity results from a backbone carbonyl interaction of Lys305' with the 6-NH2 group of adenine in the A site and a Ser347 Ogamma interaction with the 2-NH2 group of guanine in the C site. Steric considerations favor binding of the nucleoside diphosphate to the A site. Site-directed replacements of key residues increased the nucleotide concentrations needed for 50% inhibition and in some cases perturbed synergism. Mutations in either of the nucleotide sites perturbed function at both sites, supporting the important role of synergism.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19706171 K.Lakomek, A.Dickmanns, M.Kettwig, H.Urlaub, R.Ficner, and T.Lübke (2009).
Initial insight into the function of the lysosomal 66.3 kDa protein from mouse by means of X-ray crystallography.
  BMC Struct Biol, 9, 56.
PDB codes: 3fgr 3fgt 3fgw
18948259 R.L.Switzer (2009).
Discoveries in bacterial nucleotide metabolism.
  J Biol Chem, 284, 6585-6594.  
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
17951049 S.Mouilleron, and B.Golinelli-Pimpaneau (2007).
Conformational changes in ammonia-channeling glutamine amidotransferases.
  Curr Opin Struct Biol, 17, 653-664.  
16204483 A.Jiménez, M.A.Santos, M.Pompejus, and J.L.Revuelta (2005).
Metabolic engineering of the purine pathway for riboflavin production in Ashbya gossypii.
  Appl Environ Microbiol, 71, 5743-5751.  
15870345 J.A.Kloepfer, R.E.Mielke, and J.L.Nadeau (2005).
Uptake of CdSe and CdSe/ZnS quantum dots into bacteria via purine-dependent mechanisms.
  Appl Environ Microbiol, 71, 2548-2557.  
15716449 P.Chander, K.M.Halbig, J.K.Miller, C.J.Fields, H.K.Bonner, G.K.Grabner, R.L.Switzer, and J.L.Smith (2005).
Structure of the nucleotide complex of PyrR, the pyr attenuation protein from Bacillus caldolyticus, suggests dual regulation by pyrimidine and purine nucleotides.
  J Bacteriol, 187, 1773-1782.
PDB codes: 1non 1xz8 1xzn
16152602 P.H.Rehse, and T.H.Tahirov (2005).
Crystal structure of a purine/pyrimidine phosphoribosyltransferase-related protein from Thermus thermophilus HB8.
  Proteins, 61, 658-665.
PDB codes: 1vch 2cvb
12037295 A.Kadziola, J.Neuhard, and S.Larsen (2002).
Structure of product-bound Bacillus caldolyticus uracil phosphoribosyltransferase confirms ordered sequential substrate binding.
  Acta Crystallogr D Biol Crystallogr, 58, 936-945.
PDB code: 1i5e
10850988 A.K.Bera, S.Chen, J.L.Smith, and H.Zalkin (2000).
Temperature-dependent function of the glutamine phosphoribosylpyrophosphate amidotransferase ammonia channel and coupling with glycinamide ribonucleotide synthetase in a hyperthermophile.
  J Bacteriol, 182, 3734-3739.  
  10049369 S.Li, J.L.Smith, and H.Zalkin (1999).
Mutational analysis of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase propeptide processing.
  J Bacteriol, 181, 1403-1408.  
  9514258 C.R.Muchmore, J.M.Krahn, J.H.Kim, H.Zalkin, and J.L.Smith (1998).
Crystal structure of glutamine phosphoribosylpyrophosphate amidotransferase from Escherichia coli.
  Protein Sci, 7, 39-51.
PDB codes: 1ecf 1ecj
  9551555 D.R.Tomchick, R.J.Turner, R.L.Switzer, and J.L.Smith (1998).
Adaptation of an enzyme to regulatory function: structure of Bacillus subtilis PyrR, a pyr RNA-binding attenuation protein and uracil phosphoribosyltransferase.
  Structure, 6, 337-350.
PDB codes: 1a3c 1a4x
9914248 J.L.Smith (1998).
Glutamine PRPP amidotransferase: snapshots of an enzyme in action.
  Curr Opin Struct Biol, 8, 686-694.  
9333323 J.M.Krahn, J.H.Kim, M.R.Burns, R.J.Parry, H.Zalkin, and J.L.Smith (1997).
Coupled formation of an amidotransferase interdomain ammonia channel and a phosphoribosyltransferase active site.
  Biochemistry, 36, 11061-11068.
PDB codes: 1ecb 1ecc
  9393728 S.Chen, L.Zheng, D.R.Dean, and H.Zalkin (1997).
Role of NifS in maturation of glutamine phosphoribosylpyrophosphate amidotransferase.
  J Bacteriol, 179, 7587-7590.  
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 codes are shown on the right.