title: Expression study of mutant cystathionine beta-synthase found in Japanese patients with homocystinuria.
abstract: Cystathionine beta-synthase (CBS) deficiency is the most common cause of homocystinuria. More than 130 pathogenic mutations, mostly in the Caucasian populations, have been described. Recently, our group reported a mutation analysis of Japanese homocystinuric patients. In the present paper, we report an expression study of several mutant CBS enzymes in Escherichia coli, i.e., R121H, G148R, G151R, S217F, H232D, R266G, 1591delTTCG, and K441X. All of the mutants except K441X exhibited severely decreased activity, and the capability to form tetramers of most mutants was severely impaired. The K441X mutant, on the other hand, exhibited relatively high activity (63% of the wild type activity). This was probably due to two factors. First, the high abundance of the full-length CBS protein, a likely K441Q mutant, which was produced through suppression of the amber termination codon by glutamine tRNA in E. coli. And second, the presence of a C-terminally truncated protein, which was previously shown to be constitutively activated. Patient-derived lymphocytes, however, showed no detectable CBS subunits. As previously hypothesized, the increased aggregation of mutant CBS subunits might be a common pathogenic mechanism in CBS deficiency.
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Katsushima
authors.forename: Jana
authors.initials: J
authors.lastname: Oliveriusova
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Kazuie
authors.initials: K
authors.lastname: Iinuma
authors.forename: Eva
authors.initials: E
authors.lastname: Kraus
authors.forename: Renata
authors.initials: R
authors.lastname: Stouracova
authors.forename: Jan P
authors.initials: JP
authors.lastname: Kraus
mesh_terms: D000328:Adult; D044466:Asian People; D002675:Child, Preschool; D003541:Cystathionine beta-Synthase / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006712:Homocystinuria / Q000201:enzymology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D009154:Mutation
chemical_list: D003541:Cystathionine beta-Synthase