Expression study of mutant cystathionine β-synthase found in Japanese patients with homocystinuria

Fumio Katsushima, Jana Oliveriusova, Osamu Sakamoto, Toshihiro Ohura, Yoshiaki Kondo, Kazuie Iinuma, Eva Kraus, Renata Stouracova, Jan P. Kraus

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12 Citations (Scopus)


Cystathionine β-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.

Original languageEnglish
Pages (from-to)323-328
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number4
Publication statusPublished - 2006 Apr
Externally publishedYes


  • Cystathionine β-synthase
  • Expression study
  • Homocystinuria

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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