title: A novel point mutation (I137T) in the conserved 5-phosphoribosyl-1-pyrophosphate binding motif of hypoxanthine-guanine phosphoribosyltransferase (HPRTJerusalem) in a variant of Lesch-Nyhan syndrome.
abstract: We identified a novel point mutation (I137T) in the hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) encoding gene, in a patient with partial deficiency of the enzyme (variant of Lesch-Nyhan syndrome). The mutation, ATT to ACT, resulting in substitution of isoleucine to threonine, occurred at codon 137 (exon 6), which is within the region encoding the binding site for 5-phosphoribosyl-1-pyrophosphate (PRPP). We suggest the mechanism by which the mutation-induced structural alteration of HPRT reduced the affinity of the enzyme for PRPP.
authors.affiliation: Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. shanie@post.tau.ac.il
authors.forename: Esther
authors.initials: E
authors.lastname: Zoref-Shani
authors.forename: Yael
authors.initials: Y
authors.lastname: Bromberg
authors.forename: Joel
authors.initials: J
authors.lastname: Hirsch
authors.forename: Sofia
authors.initials: S
authors.lastname: Feinstein
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Frishberg
authors.forename: Oded
authors.initials: O
authors.lastname: Sperling
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D007926:Lesch-Nyhan Syndrome / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D017354:Point Mutation; D011247:Pregnancy
chemical_list: D017931:DNA Primers; D010754:Phosphoribosyl Pyrophosphate; D007041:Hypoxanthine Phosphoribosyltransferase