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From Proteopedia
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=Introduction= | =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 | + | 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. <ref name="Shi"> PMID:10360366 </ref> |
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<Structure load='1bzy' size='200' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | <Structure load='1bzy' size='200' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
| - | = | + | =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 loop 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. | |
RCSB Protein Data Bank <ref name="Shi"> PMID:10360366 </ref> | RCSB Protein Data Bank <ref name="Shi"> PMID:10360366 </ref> | ||
=Section 1.2= | =Section 1.2= | ||
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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 loop 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. RCSB Protein Data Bank [1]
Section 1.2
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
