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PDBsum entry 1fsg

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1fsg
Jmol
Contents
Protein chains
233 a.a. *
Ligands
PRP ×2
9DG ×2
Metals
_MG ×4
Waters ×939
* Residue conservation analysis
PDB id:
1fsg
Name: Transferase
Title: Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransfe complexed with 9-deazaguanine, alpha-d-5-phosphoribosyl-1- pyrophosphate (prpp) and two mg2+ ions
Structure: Hypoxanthine-guanine phosphoribosyltransferase. Chain: a, c. Synonym: hgprtase. Engineered: yes
Source: Toxoplasma gondii. Organism_taxid: 383379. Strain: rh. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
Resolution:
1.05Å     R-factor:   0.122     R-free:   0.154
Authors: A.Heroux,E.L.White,L.J.Ross,A.P.Kuzin,D.W.Borhani
Key ref:
A.Héroux et al. (2000). Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis. Structure, 8, 1309-1318. PubMed id: 11188695 DOI: 10.1016/S0969-2126(00)00546-3
Date:
08-Sep-00     Release date:   06-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q26997  (HGXR_TOXGO) -  Hypoxanthine-guanine-xanthine phosphoribosyltransferase
Seq:
Struc:
230 a.a.
233 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     nucleoside metabolic process   5 terms 
  Biochemical function     nucleotide binding     5 terms  

 

 
DOI no: 10.1016/S0969-2126(00)00546-3 Structure 8:1309-1318 (2000)
PubMed id: 11188695  
 
 
Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis.
A.Héroux, E.L.White, L.J.Ross, A.P.Kuzin, D.W.Borhani.
 
  ABSTRACT  
 
BACKGROUND: Hypoxanthine-guanine phosphoribosyltransferases (HGPRTs) are well-recognized antiparasitic drug targets. HGPRT is also a paradigmatic representative of the phosphoribosyltransferase family of enzymes, which includes other important biosynthetic and salvage enzymes and drug targets. To better understand the reaction mechanism of this enzyme, we have crystallized HGPRT from the apicomplexan protozoan Toxoplasma gondii as a ternary complex with a substrate and a substrate analog. RESULTS: The crystal structure of T. gondii HGPRT with the substrate Mg2+-PRPP and a nonreactive substrate analog, 9-deazaguanine, bound in the active site has been determined at 1.05 A resolution and refined to a free R factor of 15.4%. This structure constitutes the first atomic-resolution structure of both a phosphoribosyltransferase and the central metabolic substrate PRPP. This pre-transition state complex provides a clearer understanding of the structural basis for catalysis by HGPRT. CONCLUSIONS: Three types of substrate deformation, chief among them an unexpected C2'-endo pucker adopted by the PRPP ribose ring, raise the energy of the ground state. A cation-pi interaction between Tyr-118 and the developing oxocarbenium ion in the ribose ring helps to stabilize the transition state. Enforced substrate propinquity coupled with optimal reactive geometry for both the substrates and the active site residues with which they interact contributes to catalysis as well.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The Chemical Reaction Catalyzed by HGPRT

 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1309-1318) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20170081 H.Deng, R.Callender, V.L.Schramm, and C.Grubmeyer (2010).
Pyrophosphate activation in hypoxanthine--guanine phosphoribosyltransferase with transition state analogue.
  Biochemistry, 49, 2705-2714.  
17266529 J.E.Hyde (2007).
Targeting purine and pyrimidine metabolism in human apicomplexan parasites.
  Curr Drug Targets, 8, 31-47.  
17894860 P.S.Monzani, S.Trapani, O.H.Thiemann, and G.Oliva (2007).
Crystal structure of Leishmania tarentolae hypoxanthine-guanine phosphoribosyltransferase.
  BMC Struct Biol, 7, 59.
PDB code: 1pzm
16714288 M.Marino, M.Deuss, D.I.Svergun, P.V.Konarev, R.Sterner, and O.Mayans (2006).
Structural and mutational analysis of substrate complexation by anthranilate phosphoribosyltransferase from Sulfolobus solfataricus.
  J Biol Chem, 281, 21410-21421.
PDB codes: 1zxy 1zyk 2gvq
15272157 A.W.Schüttelkopf, and D.M.van Aalten (2004).
PRODRG: a tool for high-throughput crystallography of protein-ligand complexes.
  Acta Crystallogr D Biol Crystallogr, 60, 1355-1363.  
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
11900545 C.Bashor, J.M.Denu, R.G.Brennan, and B.Ullman (2002).
Kinetic mechanism of adenine phosphoribosyltransferase from Leishmania donovani.
  Biochemistry, 41, 4020-4031.  
12070315 L.W.Guddat, S.Vos, J.L.Martin, D.T.Keough, and J.de Jersey (2002).
Crystal structures of free, IMP-, and GMP-bound Escherichia coli hypoxanthine phosphoribosyltransferase.
  Protein Sci, 11, 1626-1638.
PDB codes: 1g9s 1g9t 1grv
12171925 W.Shi, A.E.Sarver, C.C.Wang, K.S.Tanaka, S.C.Almo, and V.L.Schramm (2002).
Closed site complexes of adenine phosphoribosyltransferase from Giardia lamblia reveal a mechanism of ribosyl migration.
  J Biol Chem, 277, 39981-39988.
PDB codes: 1l1q 1l1r
11854281 W.Versées, K.Decanniere, E.Van Holsbeke, N.Devroede, and J.Steyaert (2002).
Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax.
  J Biol Chem, 277, 15938-15946.
PDB codes: 1kic 1kie
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.