› 4ijq

X-ray diffraction
2Å resolution

Human hypoxanthine-guanine phosphoribosyltransferase in complex with [(2-((Guanine-9H-yl)methyl)propane-1,3-diyl)bis(oxy)]bis(methylene))diphosphonic acid

Released:
DOI: 10.2210/pdb4ijq/pdb
PDB entry 4ijq coloured by chain, front view.
PDB entry 4ijq coloured by chain, side view.
PDB entry 4ijq coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Acyclic nucleoside phosphonates containing a second phosphonate group are potent inhibitors of 6-oxopurine phosphoribosyltransferases and have antimalarial activity.
Keough DT, Špaček P, Hocková D, Tichý T, Vrbková S, Slavětínská L, Janeba Z, Naesens L, Edstein MD, Chavchich M, Wang TH, de Jersey J, Guddat LW
J Med Chem 56 2513-26 (2013)
PMID: 23448281

Function and Biology Details

Reaction catalysed: 
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo tetramer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-132564 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Hypoxanthine-guanine phosphoribosyltransferase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 223 amino acids
Theoretical weight: 25.31 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P00492 (Residues: 2-218; Coverage: 100%)
Gene names: HPRT, HPRT1
Sequence domains: Phosphoribosyl transferase domain
Structure domains: Rossmann fold

Ligands and Environments

3 bound ligands:
Ligand SV2 4 x SV2
Ligand SO4 4 x SO4
Ligand MG 8 x MG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: AUSTRALIAN SYNCHROTRON BEAMLINE MX1
Spacegroup: P21
Unit cell:
a: 56.505Å b: 127.741Å c: 64.756Å
α: 90° β: 102.01° γ: 90°
R-values:
R R work R free
0.175 0.173 0.223
Expression system: Escherichia coli

Quick links

Citations

5 review citations

Prodrugs of phosphonates and phosphates: crossing the membrane barrier.
Wiemer et al. (2015)
4 more

1 mention without citation

Evaluation of the Trypanosoma brucei 6-oxopurine salvage pathway as a potential target for drug discovery.
Doleželová et al. (2018)