Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We defined the amino acid sequence of adenine phosphoribosyltransferase isolated from human erythrocytes. Peptide fragments formed by cleavage at arginine, lysine, glutamic acid, and methionine were purified by high pressure liquid chromatography and sequenced by manual Edman degradation. The complete primary structure of human adenine phosphoribosyltransferase was established by sequence analysis of 19 peptide fragments. Presumed homology between the human and rodent enzymes was used to order fragments that had inadequate overlapping sequences. The enzyme has 179 residues with a calculated subunit molecular weight of 19,481. Mass spectrometry indicated that the NH2-terminal residue is acetylated. Human adenine phosphoribosyltransferase has sequence homology with xanthine-guanine phosphoribosyltransferase from Escherichia coli in 110-amino acid region encompassing the NH2-terminal section of the enzyme.
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PMID:Human adenine phosphoribosyltransferase. Complete amino acid sequence of the erythrocyte enzyme. 353 Dec 9

The entire amino acid sequence of hypoxanthine-guanine phosphoribosyltransferase from human erythrocytes has been defined. Peptide fragments formed by cleavage at arginine, glutamic acid, and methionine residues were analyzed by Edman degradation or digestion with carboxypeptidase. The complete primary structure of human hypoxanthine-guanine phosphoribosyltransferase was established by sequence analysis of 17 peptide fragments, 15 of which were purified by reverse-phase high pressure liquid chromatography. The enzyme is 217 residues long with a molecular weight equal to 24,470. Mass spectroscopy indicated that the NH2-terminal alanine is acetylated.
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PMID:Human hypoxanthine-guanine phosphoribosyltransferase. Complete amino acid sequence of the erythrocyte enzyme. 710 41

Lesch-Nyhan syndrome is associated with complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), characterized by hyperuricemia and severe neurological signs. The HPRT gene has been mapped to the q26 region on the long arm of the X-chromosome. We are taking care of a family of Lesch-Nyhan syndrome. A 14-year-old male was noted the growth disturbance at the age of 7 months and self-mutilation behavior characterized by compulsive biting of his lip and fingers at the age of 18 months. In 1987, at the age of 4, he was diagnosed as Lesch-Nyhan syndrome from neurologic signs and hyperuricemia (9.8 mg/dl). Neurological examination revealed mild mental and growth retardation, spasticity and hyperreflexia of lower extremities, choreoathetoid movements of extremities, and compulsive self-mutilation. The HPRT activity in erythrocytes of this patient was 0.02 nmol/min/mg hemoglobin (control value 1.76 +/- 0.06), and adenine phosphoribosyltransferase (APRT) activity was 1.08 nmol/min/mg hemoglobin (control value 0.43 +/- 0.06). Using polymerase chain reaction (PCR) method coupled with direct sequencing, we analyzed the nucleotide sequences of each exon from the genomic DNA as well as the entire HPRT coding region of the cDNA by RT-PCR method. In the HPRT gene from the patient, a guanine to adenine substitution at base position 209 in exon 3 was identified, which resulted in a single amino acid substitution of glycine with glutamic acid at codon 70. The family studies indicated that his mother, sister and grandmother were heterozygotes. PCR-restriction fragment length polymorphism (RFLP) utilizing Mnl I site which created by the mutation, was useful for detection of the mutant gene. We have identified a new missense mutation of the HPRT gene in a Japanese patient. This mutation was reported at the same codon as foreign mutants and mighty be indicative of a location of mutation activity in the HPRT gene.
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PMID:[A Japanese family with Lesch-Nyhan syndrome resulting from a new point mutation in hypoxanthine-guanine phosphoribosyltransferase gene]. 939 32

The mutation in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene has been determined in two brothers affected with Lesch-Nyhan syndrome. Female members of the family who are at risk for being heterozygous carriers of the HPRT mutation were also studied to determine whether they carry the mutation. DNA sequencing revealed that the boys' mother is heterozygous for the mutation in her somatic cells, but that three maternal aunts are not heterozygous. Such carrier information is important for the future pregnancy plans of at-risk females. The mutation, an A-->T transversion at cDNA base 590 (590A-->T), results in an amino acid change of glutamic acid to valine at codon 197, and has not been reported previously in a Lesch-Nyhan syndrome male. This mutation is designated HPRTBrasil.
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PMID:Identification of a new Lesch-Nyhan syndrome mutation (HPRTBrasil) and analysis of potentially heterozygous females. 1068 77

The role of an invariant aspartic acid (Asp137) in hypoxanthine phosphoribosyltransferases (HPRTs) was examined by site-directed and saturation mutagenesis, functional analysis, and X-ray crystallography using the HPRT from Trypanosoma cruzi. Alanine substitution (D137A) resulted in a 30-fold decrease of k(cat), suggesting that Asp137 participates in catalysis. Saturation mutagenesis was used to generate a library of mutant HPRTs with random substitutions at position 137, and active enzymes were identified by complementation of a bacterial purine auxotroph. Functional analyses of the mutants, including determination of steady-state kinetic parameters and pH-rate dependence, indicate that glutamic acid or glutamine can replace the wild-type aspartate. However, the catalytic efficiency and pH-rate profile for the structural isosteric mutant, D137N, were similar to the D137A mutant. Crystal structures of four of the mutant enzymes were determined in ternary complex with substrate ligands. Structures of the D137E and D137Q mutants reveal potential hydrogen bonds, utilizing several bound water molecules in addition to protein atoms, that position these side chains within hydrogen bond distance of the bound purine analogue, similar in position to the aspartate in the wild-type structure. The crystal structure of the D137N mutant demonstrates that the Asn137 side chain does not form interactions with the purine substrate but instead forms novel interactions that cause the side chain to adopt a nonfunctional rotamer. The results from these structural and functional analyses demonstrate that HPRTs do not require a general base at position 137 for catalysis. Instead, hydrogen bonding sufficiently stabilizes the developing partial positive charge at the N7-atom of the purine substrate in the transition-state to promote catalysis.
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PMID:The role for an invariant aspartic acid in hypoxanthine phosphoribosyltransferases is examined using saturation mutagenesis, functional analysis, and X-ray crystallography. 1125 86