Molecular defect of isovaleryl-CoA dehydrogenase in the skunk mutant of silkworm, Bombyx mori

Kei Urano, Takaaki Daimon, Yutaka Banno, Kazuei Mita, Tohru Terada, Kentaro Shimizu, Susumu Katsuma, Toru Shimada

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

The isovaleric acid-emanating silkworm mutant skunk (sku) was first studied over 30 years ago because of its unusual odour and prepupal lethality. Here, we report the identification and characterization of the gene responsible for the sku mutant. Because of its specific features and symptoms similar to human isovaleryl-CoA dehydrogenase (IVD) deficiency, also known as isovaleric acidaemia, IVD dysfunction in silkworms was predicted to be responsible for the phenotype of the sku mutant. Linkage analysis revealed that the silkworm IVD gene (BmIVD) was closely linked to the odorous phenotype as expected, and a single amino acid substitution (G376V) was found in BmIVD of the sku mutant. To investigate the effect of the G376V substitution on BmIVD function, wild-type and sku-type recombinants were constructed with a baculovirus expression system and the subsequent enzyme activity of sku-type BmIVD was shown to be significantly reduced compared with that of wild-type BmIVD. Molecular modelling suggested that this reduction in the enzyme activity may be due to negative effects of G376V mutation on FAD-binding or on monomer-monomer interactions. These observations strongly suggest that BmIVD is responsible for the sku locus and that the molecular defect in BmIVD causes the characteristic smell and prepupal lethality of the sku mutant. To our knowledge, this is, aside from humans, the first characterization of IVD deficiency in metazoa. Considering that IVD acts in the third step of leucine degradation and the sku mutant accumulates branched-chain amino acids in haemolymph, this mutant may be useful in the investigation of unique branched-chain amino acid catabolism in insects.

元の言語英語
ページ(範囲)4452-4463
ページ数12
ジャーナルFEBS Journal
277
発行部数21
DOI
出版物ステータス出版済み - 11 1 2010

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Isovaleryl-CoA Dehydrogenase
Mephitidae
Bombyx
Defects
Branched Chain Amino Acids
Enzyme activity
Substitution reactions
Genes
Monomers
Flavin-Adenine Dinucleotide
Molecular modeling
Odors
Leucine
Phenotype
Amino Acids
Hemolymph
Smell
Degradation
Baculoviridae
Enzymes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Molecular defect of isovaleryl-CoA dehydrogenase in the skunk mutant of silkworm, Bombyx mori. / Urano, Kei; Daimon, Takaaki; Banno, Yutaka; Mita, Kazuei; Terada, Tohru; Shimizu, Kentaro; Katsuma, Susumu; Shimada, Toru.

:: FEBS Journal, 巻 277, 番号 21, 01.11.2010, p. 4452-4463.

研究成果: ジャーナルへの寄稿記事

Urano, K, Daimon, T, Banno, Y, Mita, K, Terada, T, Shimizu, K, Katsuma, S & Shimada, T 2010, 'Molecular defect of isovaleryl-CoA dehydrogenase in the skunk mutant of silkworm, Bombyx mori', FEBS Journal, 巻. 277, 番号 21, pp. 4452-4463. https://doi.org/10.1111/j.1742-4658.2010.07832.x
Urano, Kei ; Daimon, Takaaki ; Banno, Yutaka ; Mita, Kazuei ; Terada, Tohru ; Shimizu, Kentaro ; Katsuma, Susumu ; Shimada, Toru. / Molecular defect of isovaleryl-CoA dehydrogenase in the skunk mutant of silkworm, Bombyx mori. :: FEBS Journal. 2010 ; 巻 277, 番号 21. pp. 4452-4463.
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AU - Urano, Kei

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AU - Banno, Yutaka

AU - Mita, Kazuei

AU - Terada, Tohru

AU - Shimizu, Kentaro

AU - Katsuma, Susumu

AU - Shimada, Toru

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