Arg452 substitution of the erythroid-specific 5-aminolaevulinate synthase, a hot spot mutation in X-linked sideroblastic anaemia, does not itself affect enzyme activity

Kazumichi Furuyama, Hideo Harigae, Tom Heller, Ben C.J. Hamel, Elisabeth I. Minder, Toru Shimizu, Tadao Kuribara, Nicole Blijlevens, Shigeki Shibahara, Shigeru Sassa

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mutations of the erythroid-specific 5-aminolaevulinate synthase (ALAS2) gene are known to be responsible for X-linked sideroblastic anaemia (XLSA). An amino acid (AA) substitution for arginine at the 452 AA position of the ALAS2 protein is the most frequent mutation, which has been found in approximately one-quarter of patients with XLSA. Despite its high frequency, there has been no report on the enzymatic activity of Arg452 mutant proteins. In this study, we examined enzymatic activity in vitro of two Arg452 mutants, Arg452Cys and Arg452His, which were found in two new pedigrees of XLSA. While these mutations must be responsible for the clinical phenotype of XLSA in patients, the enzymatic activity and stability of these mutant proteins studied in vitro are indistinguishable from those of the wild type protein. These findings suggest that the Arg452 mutation of the ALAS2 gene by itself does not decrease the enzymatic activity or the stability in vitro, and that there may be an additional factor(s) in the bone marrow, which ensures the full ALAS2 activity in vivo.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalEuropean Journal of Haematology
Volume76
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1

Keywords

  • 5-aminolaevulinate synthase
  • Genetic disorders
  • Sideroblastic anaemia
  • X-linked inheritance

ASJC Scopus subject areas

  • Hematology

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