PDBsum entry 1dku

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Transferase PDB id
Protein chains
295 a.a. *
AP2 ×2
ABM ×2
Waters ×180
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structures of bacillus subtilis phosphoribosylpyrophosphate synthetase: molecular basis of allosteric inhibition and activation.
Structure: Protein (phosphoribosyl pyrophosphate synthetase). Chain: a, b. Synonym: ribose-phosphate pyrophosphokinase. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hexamer (from PQS)
2.20Å     R-factor:   0.198     R-free:   0.241
Authors: T.A.Eriksen,A.Kadziola,A.-K.Bentsen,K.W.Harlow,S.Larsen
Key ref:
T.A.Eriksen et al. (2000). Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase. Nat Struct Biol, 7, 303-308. PubMed id: 10742175 DOI: 10.1038/74069
08-Dec-99     Release date:   05-Apr-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P14193  (KPRS_BACSU) -  Ribose-phosphate pyrophosphokinase
317 a.a.
295 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Ribose-phosphate diphosphokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Ribose activation
      Reaction: ATP + D-ribose 5-phosphate = AMP + 5-phospho-alpha-D-ribose 1-diphosphate
+ D-ribose 5-phosphate
Bound ligand (Het Group name = AP2)
matches with 78.00% similarity
+ 5-phospho-alpha-D-ribose 1-diphosphate
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 biosynthetic process   6 terms 
  Biochemical function     nucleotide binding     7 terms  


DOI no: 10.1038/74069 Nat Struct Biol 7:303-308 (2000)
PubMed id: 10742175  
Structural basis for the function of Bacillus subtilis phosphoribosyl-pyrophosphate synthetase.
T.A.Eriksen, A.Kadziola, A.K.Bentsen, K.W.Harlow, S.Larsen.
Here we report the first three-dimensional structure of a phosphoribosylpyrophosphate (PRPP) synthetase. PRPP is an essential intermediate in several biosynthetic pathways. Structures of the Bacillus subtilis PRPP synthetase in complex with analogs of the activator phosphate and the allosteric inhibitor ADP show that the functional form of the enzyme is a hexamer. The individual subunits fold into two domains, both of which resemble the type I phosphoribosyltransfereases. The active site is located between the two domains and includes residues from two subunits. Phosphate and ADP bind to the same regulatory site consisting of residues from three subunits of the hexamer. In addition to identifying residues important for binding substrates and effectors, the structures suggest a novel mode of allosteric regulation.
  Selected figure(s)  
Figure 2.
Figure 2. Overall fold, topology and quaternary structure of PRPP synthetase a, Ribbon diagram of the monomer from the SO[4]^ 2- -PRPP synthetase structure^36, 37. The N-terminal domain is at the top. Both domains contain a five-stranded parallel -sheet (gray) with two -helices on each side (blue) and a flag region (green). In addition, the N-terminal domain includes a 3[10]-helix (red) and the flexible loop (yellow). In the C-terminal domain the R5P binding loop and the PP binding loop are shown in cyan and magenta, respectively. b, Topology of the PRPP synthetase monomer with the same color scheme as in a. The numbers on the diagram refer to the nomenclature of the secondary structure shown in Fig. 1. c, MOLSCRIPT36 drawing of the hexamer from the mADP -PRPP synthetase structure composed of three pairs of independent molecules. The subunits related by the crystallographic three-fold axis are depicted in the same color with subunit A colored as in (a). The mADP molecules at the allosteric sites are shown in green, and the mAMP moieties at the ATP binding sites are shown in red. Sulfate ions as observed in the SO[4]^2- -PRPP synthetase structure are superimposed in black.
Figure 4.
Figure 4. Stereo views of the catalytic and regulatory sites a, The catalytic sites for ATP and R5P in the mADP -PRPP synthetase structure. In the SO[4]^2- -PRPP synthetase structure the R5P site is occupied by sulfate, which is superimposed onto this mADP -PRPP synthetase structure. b, The regulatory site (ADP binding site) of the mADP -PRPP synthetase structure occupied by mADP. The sulfate found at the ADP site in the SO[4]^2- -PRPP synthetase structure is superimposed; this sulfate occupies the -phosphate position of the ADP site. These illustrations were produced using MOLSCRIPT36.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 303-308) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21045009 L.J.Alderwick, G.S.Lloyd, A.J.Lloyd, A.L.Lovering, L.Eggeling, and G.S.Besra (2011).
Biochemical characterization of the Mycobacterium tuberculosis phosphoribosyl-1-pyrophosphate synthetase.
  Glycobiology, 21, 410-425.  
21085589 A.P.Lucarelli, S.Buroni, M.R.Pasca, M.Rizzi, A.Cavagnino, G.Valentini, G.Riccardi, and L.R.Chiarelli (2010).
Mycobacterium tuberculosis phosphoribosylpyrophosphate synthetase: biochemical features of a crucial enzyme for mycobacterial cell wall biosynthesis.
  PLoS One, 5, e15494.  
20380929 Brouwer, H.van Bokhoven, S.B.Nabuurs, W.F.Arts, J.Christodoulou, and J.Duley (2010).
PRPS1 mutations: four distinct syndromes and potential treatment.
  Am J Hum Genet, 86, 506-518.  
19959576 M.J.Koenigsknecht, L.A.Fenlon, and D.M.Downs (2010).
Phosphoribosylpyrophosphate synthetase (PrsA) variants alter cellular pools of ribose 5-phosphate and influence thiamine synthesis in Salmonella enterica.
  Microbiology, 156, 950-959.  
20021999 X.Liu, D.Han, J.Li, B.Han, X.Ouyang, J.Cheng, X.Li, Z.Jin, Y.Wang, M.Bitner-Glindzicz, X.Kong, H.Xu, A.Kantardzhieva, R.D.Eavey, C.E.Seidman, J.G.Seidman, L.L.Du, Z.Y.Chen, P.Dai, M.Teng, D.Yan, and H.Yuan (2010).
Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2.
  Am J Hum Genet, 86, 65-71.  
18948259 R.L.Switzer (2009).
Discoveries in bacterial nucleotide metabolism.
  J Biol Chem, 284, 6585-6594.  
18782443 A.Jiménez, M.A.Santos, and J.L.Revuelta (2008).
Phosphoribosyl pyrophosphate synthetase activity affects growth and riboflavin production in Ashbya gossypii.
  BMC Biotechnol, 8, 67.  
18422659 B.A.Wolucka (2008).
Biosynthesis of D-arabinose in mycobacteria - a novel bacterial pathway with implications for antimycobacterial therapy.
  FEBS J, 275, 2691-2711.  
17701900 H.J.Kim, K.M.Sohn, M.E.Shy, K.M.Krajewski, M.Hwang, J.H.Park, S.Y.Jang, H.H.Won, B.O.Choi, S.H.Hong, B.J.Kim, Y.L.Suh, C.S.Ki, S.Y.Lee, S.H.Kim, and J.W.Kim (2007).
Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5).
  Am J Hum Genet, 81, 552-558.  
16008562 B.Hove-Jensen, A.K.Bentsen, and K.W.Harlow (2005).
Catalytic residues Lys197 and Arg199 of Bacillus subtilis phosphoribosyl diphosphate synthase. Alanine-scanning mutagenesis of the flexible catalytic loop.
  FEBS J, 272, 3631-3639.  
  16508088 H.B.Napolitano, S.A.Sculaccio, O.H.Thiemann, and G.Oliva (2005).
Preliminary crystallographic analysis of sugar cane phosphoribosylpyrophosphate synthase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 49-51.  
15752360 K.F.Jensen, S.Arent, S.Larsen, and L.Schack (2005).
Allosteric properties of the GTP activated and CTP inhibited uracil phosphoribosyltransferase from the thermoacidophilic archaeon Sulfolobus solfataricus.
  FEBS J, 272, 1440-1453.  
16051603 K.S.Champagne, M.Sissler, Y.Larrabee, S.Doublié, and C.S.Francklyn (2005).
Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog.
  J Biol Chem, 280, 34096-34104.
PDB codes: 1z7m 1z7n
15935511 M.Kilstrup, K.Hammer, P.Ruhdal Jensen, and J.Martinussen (2005).
Nucleotide metabolism and its control in lactic acid bacteria.
  FEMS Microbiol Rev, 29, 555-590.  
15689504 M.Kukimoto-Niino, R.Shibata, K.Murayama, H.Hamana, M.Nishimoto, Y.Bessho, T.Terada, M.Shirouzu, S.Kuramitsu, and S.Yokoyama (2005).
Crystal structure of a predicted phosphoribosyltransferase (TT1426) from Thermus thermophilus HB8 at 2.01 A resolution.
  Protein Sci, 14, 823-827.
PDB code: 1wd5
15560793 B.Hove-Jensen, and J.N.McGuire (2004).
Surface exposed amino acid differences between mesophilic and thermophilic phosphoribosyl diphosphate synthase.
  Eur J Biochem, 271, 4526-4533.  
15229886 N.Fernandez-Fuentes, A.Hermoso, J.Espadaler, E.Querol, F.X.Aviles, and B.Oliva (2004).
Classification of common functional loops of kinase super-families.
  Proteins, 56, 539-555.  
12847698 P.García-Pavía, R.J.Torres, M.Rivero, M.Ahmed, J.García-Puig, and M.A.Becker (2003).
Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman.
  Arthritis Rheum, 48, 2036-2041.  
11876660 H.Cao, B.L.Pietrak, and C.Grubmeyer (2002).
Quinolinate phosphoribosyltransferase: kinetic mechanism for a type II PRTase.
  Biochemistry, 41, 3520-3528.  
11839305 L.A.Martinez-Cruz, M.K.Dreyer, D.C.Boisvert, H.Yokota, M.L.Martinez-Chantar, R.Kim, and S.H.Kim (2002).
Crystal structure of MJ1247 protein from M. jannaschii at 2.0 A resolution infers a molecular function of 3-hexulose-6-phosphate isomerase.
  Structure, 10, 195-204.
PDB code: 1jeo
11604537 B.N.Krath, and B.Hove-Jensen (2001).
Implications of secondary structure prediction and amino acid sequence comparison of class I and class II phosphoribosyl diphosphate synthases on catalysis, regulation, and quaternary structure.
  Protein Sci, 10, 2317-2324.  
11435118 L.J.Baker, J.A.Dorocke, R.A.Harris, and D.E.Timm (2001).
The crystal structure of yeast thiamin pyrophosphokinase.
  Structure, 9, 539-546.
PDB code: 1ig0
11133979 Y.Hernando, A.T.Carter, S.Sickinger, and M.Schweizer (2001).
Characterization of the promoter of PRS1 in Saccharomyces cerevisiae identifies three regions potentially involved in control of expression.
  J Bacteriol, 183, 795-799.  
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.