Structure–function analysis of human protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1, POMGnT1
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- 作者：Akasaka-Manya ; Keiko ; Manya ; Hiroshi ; Kobayashi ; Kazuhiro ; Toda ; Tatsushi ; Endo ; Tamao
- 关键词：Muscle&ndash ; eye&ndash ; brain disease ; Muscular dystrophy ; Glycosyltransferase ; Catalytic domain ; Stem domain ; Mutation ; POMGnT1
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2004
- 出版时间：July 16, 2004
- 年：2004
- 卷：320
- 期：1
- 页码：39-44
- 全文大小：271 K
文摘
Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the transfer of GlcNAc to O-mannose of glycoproteins. Mutations in the POMGnT1 gene cause a type of congenital muscular dystrophy called muscle–eye–brain disease (MEB). We evaluated several truncated mutants of POMGnT1 to determine the minimal catalytic domain. Deletions of 298 amino acids in the N-terminus and 9 amino acids in the C-terminus did not affect POMGnT1 activity, while larger deletions on either end abolished activity. These data indicate that the minimal catalytic domain is at least 353 amino acids. Single amino acid substitutions in the stem domain of POMGnT1 from MEB patients abolished the activity of the membrane-bound form but not the soluble form. This suggests that the stem domain of the soluble form of POMGnT1 is unnecessary for activity, but that some amino acids play a crucial role in the membrane-bound form.