Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome.
AUTOR(ES)
Fujimori, S
RESUMO
Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) causes the Lesch-Nyhan syndrome. Previous characterization of a mutant form of HPRT, HPRTYale, from a subject with the Lesch-Nyhan syndrome revealed normal mRNA and protein concentrations, no residual catalytic activity, and cathodal migration upon PAGE. We have cloned and sequenced HPRTYale cDNA. The nucleotide sequence of full-length HPRTYale cDNA revealed a single nucleotide substitution compared with normal HPRT cDNA: G----C at nucleotide position 211. This transversion predicts substitution of arginine for glycine at amino acid position 71, explaining the cathodal migration of HPRTYale. Chou-Fasman secondary structure analysis predicts a change in the probability of beta-turn formation in the region containing the mutation. Inclusion of the bulky arginine side chain in place of glycine probably disrupts protein folding as well. Cloning mutant forms of cDNA allows identification of specific mutations, provides insight into mutational mechanisms, and facilitates structure-function analysis of mutant proteins.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=303636Documentos Relacionados
- Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome.
- Hypoxanthine-guanine phosphoribosyltransferase: characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome
- Dietary-Induced Variation of Hypoxanthine-Guanine Phosphoribosyl Transferase Activity in Patients with the Lesch-Nyhan Syndrome
- Use of phytohaemagglutinin stimulated lymphocytes to study effects of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency on polynucleotide and protein synthesis in the Lesch-Nyhan syndrome.
- THE PURINE REQUIREMENT OF CELLS CULTURED FROM HUMANS AFFECTED WITH THE LESCH-NYHAN SYNDROME (HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY)*