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.
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.
Zoref-Shani
Esther
E
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. shanie@post.tau.ac.il
Bromberg
Yael
Y
Hirsch
Joel
J
Feinstein
Sofia
S
Frishberg
Yaacov
Y
Sperling
Oded
O
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
D017931:DNA Primers; D010754:Phosphoribosyl Pyrophosphate; D007041:Hypoxanthine Phosphoribosyltransferase