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Overview for MACiE Entry M0048

Version history

General Information

EC Number: 2.4.2.8 (A member of the Transferases, Glycosyltransferases, Pentosyltransferases)

Enzyme Name: hypoxanthine phosphoribosyltransferase

Biological Species: Homo sapiens (Human)

Catalytic Chain UniprotKB Accession Codes:

  • P00492 - Hypoxanthine-guanine phosphoribosyltransferase

Representative PDB Code: 1bzy - HUMAN HGPRTASE WITH TRANSITION STATE INHIBITOR (Resolution = 2.00 Å).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

Image of 5-phospho-alpha-D-ribose-1-diphosphate

Image of guanine

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Image of proton

Image of diphosphate

Image of GMP

5-phospho-alpha-D-ribose-1-diphosphate
C00119
CHEBI:58017
guanine
C00242
CHEBI:16235
proton
C00080
CHEBI:24636
diphosphate
C00013
CHEBI:18361
GMP
C00144
CHEBI:58115

Overall Comment: It has been suggested [3] that a general base is not required, but a strong hydrogen bond with the N7 of the purine substrate provides sufficient transition-state stabilisation to permit relatively efficient catalysis.


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Stepwise Description of the Reaction

Step 1Asp137 deprotonates the guanine which initiates a nucleophilic attack upon the C2 of the ribose ring in a substitution reaction, eliminating diphosphate.
Step 2Water deprotonates Asp137 in an inferred return step.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Glu 133 A Side Chain
Asp 134 A Side Chain
Asp 137 A Side Chain

Metal Cofactors for M0048

Type Het group Number Chain
magnesium MG 900 A Overview
magnesium MG 901 A Overview

References

  1. W. Shi et al. (1999), Nat. Struct. Biol., 6, 588-593. The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor.
    Medline: 10360366
  2. Y. Xu et al. (1998), Biochemistry, 37, 4114-4124. Catalysis in human hypoxanthine-guanine phosphoribosyltransferase: Asp 137 acts as a general acid/base.
    Medline: 9521733
  3. B. Canyuk et al. (2001), Biochemistry, 40, 2754-2765. The role for an invariant aspartic acid in hypoxanthine phosphoribosyltransferases is examined using saturation mutagenesis, functional analysis, and X-ray crystallography.
    Medline: 11258886

Homologue information for M0048 (1bzy)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

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nucleotide binding (molecular function)
magnesium ion binding (molecular function)
response to amphetamine (biological process)
hypoxanthine phosphoribosyltransferase activity (molecular function)
phosphoglucomutase activity (molecular function)
protein binding (molecular function)
soluble fraction (cellular component)
cytoplasm (cellular component)
cytosol (cellular component)
purine nucleobase metabolic process (biological process)
purine nucleotide biosynthetic process (biological process)
purine ribonucleoside salvage (biological process)
adenine salvage (biological process)
guanine salvage (biological process)
spermatogenesis (biological process)
behavior (biological process)
grooming behavior (biological process)
nucleoside metabolic process (biological process)
transferase activity, transferring glycosyl groups (molecular function)
glucose 1-phosphate metabolic process (biological process)
cytolysis (biological process)
striatum development (biological process)
cerebral cortex neuron differentiation (biological process)
central nervous system neuron development (biological process)
GMP salvage (biological process)
IMP salvage (biological process)
protein homodimerization activity (molecular function)
purine-containing compound salvage (biological process)
hypoxanthine salvage (biological process)
positive regulation of dopamine metabolic process (biological process)
GMP catabolic process (biological process)
IMP metabolic process (biological process)
adenine metabolic process (biological process)
hypoxanthine metabolic process (biological process)
lymphocyte proliferation (biological process)
dendrite morphogenesis (biological process)
protein homotetramerization (biological process)
guanine phosphoribosyltransferase activity (molecular function)
nucleobase-containing small molecule metabolic process (biological process)
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