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From Proteopedia
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=Structure= | =Structure= | ||
| - | HGPRT belongs to a group of enzymes known as phosphoribosyltransferases (PRTases), which are involved in purine, pyrimidine and amino acid synthesis. The structures of PRTases fall into two groups, type 1 and type 2. A common alpha/beta-fold called the PRPP motif and a flexible loop are structural characteristics of type 1 PRTases. Type 2 PRTases do not have a PRPP motif. The characteristic loop of type 1 PRTases closes after substrate binding and is thought to sequester the active site from solvent during catalysis. In the crystal structure of the human HGPRT-GMP complex, the loop is open and the active site is exposed to the solvent. The PRTase from the parasite, ''Toxoplasma gondii'', has a mobile loop that partially covers the active site, whereas the flexible loop in ''Trypanosoma cruzii'' does not sequester the second active site from solvent. | + | HGPRT belongs to a group of enzymes known as phosphoribosyltransferases (PRTases), which are involved in purine, pyrimidine and amino acid synthesis. The structures of PRTases fall into two groups, type 1 and type 2. A common alpha/beta-fold called the PRPP motif and a flexible loop are structural characteristics of type 1 PRTases. Type 2 PRTases do not have a PRPP motif. The characteristic loop of type 1 PRTases closes after substrate binding and is thought to sequester the active site from solvent during catalysis. In the crystal structure of the human HGPRT-GMP complex, the loop is open and the active site is exposed to the solvent. The PRTase from the parasite, ''Toxoplasma gondii'', has a mobile loop that partially covers the active site, whereas the flexible loop in ''Trypanosoma cruzii'' does not sequester the second active site from solvent. <ref name="Shi"> PMID:10360366 </ref> |
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Revision as of 02:54, 4 April 2011
| This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada. |
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Contents |
Introduction
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme in purine salvage pathways. This enzyme salvages guanine directly and adenine indirectly from catabolism. It catalyzes the reversible transfer of the phosphoribosyl group from a-D-5-phosphoribosyl 1-pyrophosphate (PRPP) to hypoxanthine or guanine forming either IMP or GMP, respectively. This reaction is dependent on a divalent magnesium cation. HGPRT is deficient in Lesch-Nyhan syndrome, a severe neurological disorder characterized by high levels of blood uric acid and uncontrollable self mutilation. A partial deficiency of the enzyme leads to gouty arthritis. [1]
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Structure
HGPRT belongs to a group of enzymes known as phosphoribosyltransferases (PRTases), which are involved in purine, pyrimidine and amino acid synthesis. The structures of PRTases fall into two groups, type 1 and type 2. A common alpha/beta-fold called the PRPP motif and a flexible loop are structural characteristics of type 1 PRTases. Type 2 PRTases do not have a PRPP motif. The characteristic loop of type 1 PRTases closes after substrate binding and is thought to sequester the active site from solvent during catalysis. In the crystal structure of the human HGPRT-GMP complex, the loop is open and the active site is exposed to the solvent. The PRTase from the parasite, Toxoplasma gondii, has a mobile loop that partially covers the active site, whereas the flexible loop in Trypanosoma cruzii does not sequester the second active site from solvent. [1]
Mechanism
References
- ↑ 1.0 1.1 Shi W, Li CM, Tyler PC, Furneaux RH, Grubmeyer C, Schramm VL, Almo SC. The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor. Nat Struct Biol. 1999 Jun;6(6):588-93. PMID:10360366 doi:http://dx.doi.org/10.1038/9376
