PDBsum entry 1z7n

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Transferase PDB id
Protein chains
313 a.a. *
203 a.a. *
PO4 ×2
PRP ×4
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Atp phosphoribosyl transferase (hiszg atp-prtase) from lactococcus lactis with bound prpp substrate
Structure: Atp phosphoribosyltransferase regulatory subunit. Chain: a, b, c, d. Engineered: yes. Atp phosphoribosyltransferase. Chain: e, f, g, h. Synonym: atp-prtase, atp-prt. Engineered: yes
Source: Lactococcus lactis. Organism_taxid: 1358. Gene: hisz. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: hisg.
Biol. unit: Octamer (from PQS)
3.25Å     R-factor:   0.247     R-free:   0.301
Authors: K.S.Champagne,M.Sissler,Y.Larrabee,S.Doublie,C.S.Francklyn
Key ref:
K.S.Champagne et al. (2005). Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog. J Biol Chem, 280, 34096-34104. PubMed id: 16051603 DOI: 10.1074/jbc.M505041200
25-Mar-05     Release date:   09-Aug-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q02147  (HISZ_LACLA) -  ATP phosphoribosyltransferase regulatory subunit
328 a.a.
313 a.a.
Protein chains
Pfam   ArchSchema ?
Q02129  (HIS1_LACLA) -  ATP phosphoribosyltransferase
208 a.a.
203 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains E, F, G, H: E.C.  - Atp phosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Histidine Biosynthesis (early stages)
      Reaction: 1-(5-phospho-beta-D-ribosyl)-ATP + diphosphate = ATP + 5-phospho-alpha-D- ribose 1-diphosphate
+ diphosphate
5-phospho-alpha-D- ribose 1-diphosphate
Bound ligand (Het Group name = PRP)
corresponds exactly
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     cellular amino acid biosynthetic process   3 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1074/jbc.M505041200 J Biol Chem 280:34096-34104 (2005)
PubMed id: 16051603  
Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog.
K.S.Champagne, M.Sissler, Y.Larrabee, S.Doublié, C.S.Francklyn.
ATP phosphoribosyl transferase (ATP-PRT) joins ATP and 5-phosphoribosyl-1-pyrophosphate (PRPP) in a highly regulated reaction that initiates histidine biosynthesis. The unusual hetero-octameric version of ATP-PRT includes four HisG(S) catalytic subunits based on the periplasmic binding protein fold and four HisZ regulatory subunits that resemble histidyl-tRNA synthetases. Here, we present the first structure of a PRPP-bound ATP-PRT at 2.9 A and provide a structural model for allosteric activation based on comparisons with other inhibited and activated ATP-PRTs from both the hetero-octameric and hexameric families. The activated state of the octameric enzyme is characterized by an interstitial phosphate ion in the HisZ-HisG interface and new contacts between the HisZ motif 2 loop and the HisG(S) dimer interface. These contacts restructure the interface to recruit conserved residues to the active site, where they activate pyrophosphate to promote catalysis. Additionally, mutational analysis identifies the histidine binding sites within a region highly conserved between HisZ and the functional HisRS. Through the oligomerization and functional re-assignment of protein domains associated with aminoacylation and phosphate binding, the HisZ-HisG octameric ATP-PRT acquired the ability to initiate the synthesis of a key metabolic intermediate in an allosterically regulated fashion.
  Selected figure(s)  
Figure 1.
The reaction catalyzed by ATP-phosphoribosyl transferase in L. lactis. The 5′-phosphoribosyl group of PRPP is transferred to ATP yielding PR-ATP and inorganic pyrophosphate (PPi). This reaction is dependant on magnesium and is inhibited by histidine, the end product of the pathway, and the cellular effectors AMP and ADP.
Figure 5.
Inter-subunit communications involved in activation/regulation of the HisZG ATP-PRTase. a, location of the interstitial phosphate ion in the interface between HisG (green) and HisZ (blue). The residues that coordinate the ion are close to a HisZ active site loop (magenta) that comprises part of the predicted histidine binding pocket. The interstitial phosphate is observed in only two of the four HisZ-HisG interfaces, namely those featuring an ordered motif 2 loop. b, interactions between the ordered HisZ motif 2 loop (blue) and the HisG dimer interface (green and gold). Motif 2 loop residues pack against strand β8 leading to the active site, whereas Arg-120 hydrogen bonds to Glu-59′ at the C-terminal end of helices α2 and α3.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 34096-34104) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20107851 R.C.Richards, C.E.Short, W.R.Driedzic, and K.V.Ewart (2010).
Seasonal changes in hepatic gene expression reveal modulation of multiple processes in rainbow smelt (Osmerus mordax).
  Mar Biotechnol (NY), 12, 650-663.  
19233924 K.H.Sippel, A.H.Robbins, R.Reutzel, S.K.Boehlein, K.Namiki, S.Goodison, M.Agbandje-McKenna, C.J.Rosser, and R.McKenna (2009).
Structural insights into the extracytoplasmic thiamine-binding lipoprotein p37 of Mycoplasma hyorhinis.
  J Bacteriol, 191, 2585-2592.
PDB code: 3eki
18445629 M.Coseno, G.Martin, C.Berger, G.Gilmartin, W.Keller, and S.Doublié (2008).
Crystal structure of the 25 kDa subunit of human cleavage factor Im.
  Nucleic Acids Res, 36, 3474-3483.
PDB codes: 3bap 3bho
18778048 Y.Cho, T.R.Ioerger, and J.C.Sacchettini (2008).
Discovery of novel nitrobenzothiazole inhibitors for Mycobacterium tuberculosis ATP phosphoribosyl transferase (HisG) through virtual screening.
  J Med Chem, 51, 5984-5992.  
17154531 K.S.Champagne, E.Piscitelli, and C.S.Francklyn (2006).
Substrate recognition by the hetero-octameric ATP phosphoribosyltransferase from Lactococcus lactis.
  Biochemistry, 45, 14933-14943.  
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.