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PDBsum entry 1hgx
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protein ligands Protein-protein interface(s) links
Transferase (glycosyltransferase) PDB id
1hgx

 

 

 

 

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Contents
Protein chains
164 a.a. *
Ligands
5GP
SO4
Waters ×134
* Residue conservation analysis
PDB id:
1hgx
Name: Transferase (glycosyltransferase)
Title: Hypoxanthine-guanine-xanthine phosphoribosyltransferase (hgxprtase)
Structure: Hypoxanthine-guanine-xanthine phosphoribosyltransferase. Chain: a, b. Synonym: hgxprtase. Engineered: yes
Source: Tritrichomonas foetus. Organism_taxid: 5724. Strain: kv1. Atcc: 30924. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.175     R-free:   0.234
Authors: J.R.Somoza,C.C.Wang,R.J.Fletterick
Key ref:
J.R.Somoza et al. (1996). Crystal structure of the hypoxanthine-guanine-xanthine phosphoribosyltransferase from the protozoan parasite Tritrichomonas foetus. Biochemistry, 35, 7032-7040. PubMed id: 8679528 DOI: 10.1021/bi953072p
Date:
12-Mar-96     Release date:   17-Aug-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P51900  (HGXR_TRIFO) -  Hypoxanthine-guanine-xanthine phosphoribosyltransferase from Tritrichomonas foetus
Seq:
Struc: 		183 a.a.
164 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.2.4.2.22  - xanthine phosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: XMP + diphosphate = xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP
 +
diphosphate
Bound ligand (Het Group name = 5GP)
matches with 92.00% similarity 		= xanthine
 + 5-phospho-alpha-D-ribose 1-diphosphate
   Enzyme class 3: E.C.2.4.2.8  - hypoxanthine phosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP
 +
diphosphate
Bound ligand (Het Group name = 5GP)
matches with 95.83% similarity 		= hypoxanthine
 + 5-phospho-alpha-D-ribose 1-diphosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/bi953072p Biochemistry 35:7032-7040 (1996)
PubMed id: 8679528  
 
 
Crystal structure of the hypoxanthine-guanine-xanthine phosphoribosyltransferase from the protozoan parasite Tritrichomonas foetus.
J.R.Somoza, M.S.Chin, P.J.Focia, C.C.Wang, R.J.Fletterick.
 
  ABSTRACT  
 
The crystal structure of the hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase) from Tritrichomonas foetus has been determined and refined against X-ray data to 1.9 A resolution. T. foetus HGXPRTase crystallizes as an asymmetric dimer, with GMP bound to only one of the two molecules that form the asymmetric unit. Each molecule of HGXPRTase is formed by two lobes joined by a short "hinge" region, and the GMP binds in a cavity between the two lobes. A comparison of the two molecules in the asymmetric unit shows that the hinge region is flexible and that ligand binding affects the relative positions of the two lobes. The binding of GMP brings the two lobes closer together, rotating one lobe by about 5 degrees relative to the other. T. foetus appears to depend on HGXPRTase for its supply of GMP, making this enzyme a target for antiparasite drug design. A comparison of the structures of T. foetus HGXPRTase and human HGPRTase reveals that, while these enzymes retain a similar polypeptide fold, there are substantial differences between the active sites of these two homologs. These differences suggest that it will be possible to find compounds that selectively inhibit the parasite enzyme.
 

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.  
18536021 P.Gayathri, I.N.Sujay Subbayya, C.S.Ashok, T.S.Selvi, H.Balaram, and M.R.Murthy (2008).
Crystal structure of a chimera of human and Plasmodium falciparum hypoxanthine guanine phosphoribosyltransferases provides insights into oligomerization.
  Proteins, 73, 1010-1020.
PDB code: 2vfa
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
17662107 Q.Chen, D.You, Y.Liang, X.Su, X.Gu, M.Luo, and X.Zheng (2007).
Crystal structure of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyl transferase L160I mutant--insights into inhibitor design.
  FEBS J, 274, 4408-4415.
PDB code: 2geb
17635220 X.Liu, W.Qian, X.Liu, H.Qin, and D.Wang (2007).
Molecular and functional analysis of hypoxanthine-guanine phosphoribosyltransferase from Arabidopsis thaliana.
  New Phytol, 175, 448-461.  
16882332 M.Duckworth, A.Ménard, F.Megraud, and G.L.Mendz (2006).
Bioinformatic analysis of Helicobacter pylori XGPRTase: a potential therapeutic target.
  Helicobacter, 11, 287-295.  
15146465 J.Duan, L.Nilsson, and B.Lambert (2004).
Structural and functional analysis of mutations at the human hypoxanthine phosphoribosyl transferase (HPRT1) locus.
  Hum Mutat, 23, 599-611.  
15262968 R.V.Dumitru, and S.W.Ragsdale (2004).
Mechanism of 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate synthase, a key enzyme in the methanopterin biosynthetic pathway.
  J Biol Chem, 279, 39389-39395.  
14501139 D.You, Q.Chen, Y.Liang, J.An, R.Li, X.Gu, M.Luo, and X.D.Su (2003).
Protein preparation, crystallization and preliminary X-ray crystallographic studies of a thermostable hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis.
  Acta Crystallogr D Biol Crystallogr, 59, 1863-1865.  
12171924 A.E.Sarver, and C.C.Wang (2002).
The adenine phosphoribosyltransferase from Giardia lamblia has a unique reaction mechanism and unusual substrate binding properties.
  J Biol Chem, 277, 39973-39980.  
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
12004061 L.J.Wallace, D.Candlish, and H.P.De Koning (2002).
Different substrate recognition motifs of human and trypanosome nucleobase transporters. Selective uptake of purine antimetabolites.
  J Biol Chem, 277, 26149-26156.  
11773618 M.A.Schumacher, C.J.Bashor, M.H.Song, K.Otsu, S.Zhu, R.J.Parry, B.Ullman, and R.G.Brennan (2002).
The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase.
  Proc Natl Acad Sci U S A, 99, 78-83.
PDB codes: 1jlr 1jls
11502531 A.M.Aronov, N.R.Munagala, I.D.Kuntz, and C.C.Wang (2001).
Virtual screening of combinatorial libraries across a gene family: in search of inhibitors of Giardia lamblia guanine phosphoribosyltransferase.
  Antimicrob Agents Chemother, 45, 2571-2576.  
11258886 B.Canyuk, P.J.Focia, and A.E.Eakin (2001).
The role for an invariant aspartic acid in hypoxanthine phosphoribosyltransferases is examined using saturation mutagenesis, functional analysis, and X-ray crystallography.
  Biochemistry, 40, 2754-2765.
PDB codes: 1i0i 1i0l 1i13 1i14
11726695 E.R.Bonner, J.N.D'Elia, B.K.Billips, and R.L.Switzer (2001).
Molecular recognition of pyr mRNA by the Bacillus subtilis attenuation regulatory protein PyrR.
  Nucleic Acids Res, 29, 4851-4865.  
11284686 N.Munagala, V.J.Basus, and C.C.Wang (2001).
Role of the flexible loop of hypoxanthine-guanine-xanthine phosphoribosyltransferase from Tritrichomonas foetus in enzyme catalysis.
  Biochemistry, 40, 4303-4311.  
10769124 A.M.Aronov, N.R.Munagala, P.R.Ortiz De Montellano, I.D.Kuntz, and C.C.Wang (2000).
Rational design of selective submicromolar inhibitors of Tritrichomonas foetus hypoxanthine-guanine-xanthine phosphoribosyltransferase.
  Biochemistry, 39, 4684-4691.  
10545170 A.Héroux, E.L.White, L.J.Ross, and D.W.Borhani (1999).
Crystal structures of the Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase-GMP and -IMP complexes: comparison of purine binding interactions with the XMP complex.
  Biochemistry, 38, 14485-14494.
PDB codes: 1qk3 1qk4
10545171 A.Héroux, E.L.White, L.J.Ross, R.L.Davis, and D.W.Borhani (1999).
Crystal structure of Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase with XMP, pyrophosphate, and two Mg(2+) ions bound: insights into the catalytic mechanism.
  Biochemistry, 38, 14495-14506.
PDB code: 1qk5
10567419 A.Jardim, S.E.Bergeson, S.Shih, N.Carter, R.W.Lucas, G.Merlin, P.J.Myler, K.Stuart, and B.Ullman (1999).
Xanthine phosphoribosyltransferase from Leishmania donovani. Molecular cloning, biochemical characterization, and genetic analysis.
  J Biol Chem, 274, 34403-34410.  
10393170 C.L.Phillips, B.Ullman, R.G.Brennan, and C.P.Hill (1999).
Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani.
  EMBO J, 18, 3533-3545.
PDB codes: 1qb7 1qb8 1qcc 1qcd
10535937 E.M.Khalil, J.De Angelis, M.Ishii, and P.A.Cole (1999).
Mechanism-based inhibition of the melatonin rhythm enzyme: pharmacologic exploitation of active site functional plasticity.
  Proc Natl Acad Sci U S A, 96, 12418-12423.  
  10338013 G.K.Balendiran, J.A.Molina, Y.Xu, J.Torres-Martinez, R.Stevens, P.J.Focia, A.E.Eakin, J.C.Sacchettini, and S.P.Craig (1999).
Ternary complex structure of human HGPRTase, PRPP, Mg2+, and the inhibitor HPP reveals the involvement of the flexible loop in substrate binding.
  Protein Sci, 8, 1023-1031.
PDB code: 1d6n
10092838 J.P.Page, N.R.Munagala, and C.C.Wang (1999).
Point mutations in the guanine phosphoribosyltransferase from Giardia lamblia modulate pyrophosphate binding and enzyme catalysis.
  Eur J Biochem, 259, 565-571.  
  10074097 J.Sauer, and P.Nygaard (1999).
Expression of the Methanobacterium thermoautotrophicum hpt gene, encoding hypoxanthine (Guanine) phosphoribosyltransferase, in Escherichia coli.
  J Bacteriol, 181, 1958-1962.  
9521670 C.C.Lee, S.P.Craig, and A.E.Eakin (1998).
A single amino acid substitution in the human and a bacterial hypoxanthine phosphoribosyltransferase modulates specificity for the binding of guanine.
  Biochemistry, 37, 3491-3498.  
  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
9914248 J.L.Smith (1998).
Glutamine PRPP amidotransferase: snapshots of an enzyme in action.
  Curr Opin Struct Biol, 8, 686-694.  
9548915 J.R.Somoza, A.G.Skillman, N.R.Munagala, C.M.Oshiro, R.M.Knegtel, S.Mpoke, R.J.Fletterick, I.D.Kuntz, and C.C.Wang (1998).
Rational design of novel antimicrobials: blocking purine salvage in a parasitic protozoan.
  Biochemistry, 37, 5344-5348.  
9628859 M.A.Schumacher, D.Carter, D.M.Scott, D.S.Roos, B.Ullman, and R.G.Brennan (1998).
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.
  EMBO J, 17, 3219-3232.
PDB codes: 1bd3 1bd4 1upf 1upu
9843428 N.R.Munagala, and C.C.Wang (1998).
Altering the purine specificity of hypoxanthine-guanine-xanthine phosphoribosyltransferase from Tritrichomonas foetus by structure-based point mutations in the enzyme protein.
  Biochemistry, 37, 16612-16619.  
9521725 N.R.Munagala, M.S.Chin, and C.C.Wang (1998).
Steady-state kinetics of the hypoxanthine-guanine-xanthine phosphoribosyltransferase from Tritrichomonas foetus: the role of threonine-47.
  Biochemistry, 37, 4045-4051.  
9860824 P.J.Focia, S.P.Craig, and A.E.Eakin (1998).
Approaching the transition state in the crystal structure of a phosphoribosyltransferase.
  Biochemistry, 37, 17120-17127.
PDB code: 1tc2
9790669 P.J.Focia, S.P.Craig, R.Nieves-Alicea, R.J.Fletterick, and A.E.Eakin (1998).
A 1.4 A crystal structure for the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi.
  Biochemistry, 37, 15066-15075.
PDB code: 1tc1
9858784 R.Nieves-Alicea, P.J.Focia, S.P.Craig, and A.E.Eakin (1998).
Limited proteolysis of a trypanosomal hypoxanthine phosphoribosyltransferase yields crystals that diffract X-rays to near atomic resolution.
  Biochim Biophys Acta, 1388, 500-505.  
  9257742 A.E.Eakin, A.Guerra, P.J.Focia, J.Torres-Martinez, and S.P.Craig (1997).
Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: crystallization and inhibition studies with purine analogs.
  Antimicrob Agents Chemother, 41, 1686-1692.  
9271497 F.G.Whitby, H.Luecke, P.Kuhn, J.R.Somoza, J.A.Huete-Perez, J.D.Phillips, C.P.Hill, R.J.Fletterick, and C.C.Wang (1997).
Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex.
  Biochemistry, 36, 10666-10674.
PDB code: 1ak5
9108251 J.Kanaani, D.Maltby, J.R.Somoza, and C.C.Wang (1997).
Inactivation of Tritrichomonas foetus and Schistosoma mansoni purine phosphoribosyltransferases by arginine-specific reagents.
  Eur J Biochem, 244, 810-817.  
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
9271502 S.Chen, D.R.Tomchick, D.Wolle, P.Hu, J.L.Smith, R.L.Switzer, and H.Zalkin (1997).
Mechanism of the synergistic end-product regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides.
  Biochemistry, 36, 10718-10726.
PDB code: 1ao0
9100006 S.Vos, J.de Jersey, and J.L.Martin (1997).
Crystal structure of Escherichia coli xanthine phosphoribosyltransferase.
  Biochemistry, 36, 4125-4134.
PDB code: 1nul
9132023 Y.Xu, J.Eads, J.C.Sacchettini, and C.Grubmeyer (1997).
Kinetic mechanism of human hypoxanthine-guanine phosphoribosyltransferase: rapid phosphoribosyl transfer chemistry.
  Biochemistry, 36, 3700-3712.  
8774725 J.Kanaani, J.R.Somoza, D.Maltby, and C.C.Wang (1996).
Probing the active site of Tritrichomonas foetus hypoxanthine-guanine-xanthine phosphoribosyltransferase using covalent modification of cysteine residues.
  Eur J Biochem, 239, 764-772.  
8836106 M.A.Schumacher, D.Carter, D.S.Ross, B.Ullman, and R.G.Brennan (1996).
Crystal structures of Toxoplasma gondii HGXPRTase reveal the catalytic role of a long flexible loop.
  Nat Struct Biol, 3, 881-887.
PDB code: 1dbr
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.

 

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