Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family
Abstract Vesicle amine transport protein-1 (VAT-1) has been implicated in the regulation of vesicular transport, mitochondrial fusion, phospholipid transport and cell migration, and is a potential target of anticancer drugs. Little is known about the molecular function of VAT-1. The amino acid seque...
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doaj-243aedf7faa34e3f9c181105aa9c440f2021-01-24T12:31:30ZengNature Publishing GroupScientific Reports2045-23222021-01-0111111310.1038/s41598-021-81409-yStructural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase familySun-Yong Kim0Tomoyuki Mori1Min Fey Chek2Shunji Furuya3Ken Matsumoto4Taisei Yajima5Toshihiko Ogura6Toshio Hakoshima7Structural Biology Laboratory, Nara Institute of Science and TechnologyStructural Biology Laboratory, Nara Institute of Science and TechnologyStructural Biology Laboratory, Nara Institute of Science and TechnologyStructural Biology Laboratory, Nara Institute of Science and TechnologyDepartment of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku UniversityStructural Biology Laboratory, Nara Institute of Science and TechnologyAbstract Vesicle amine transport protein-1 (VAT-1) has been implicated in the regulation of vesicular transport, mitochondrial fusion, phospholipid transport and cell migration, and is a potential target of anticancer drugs. Little is known about the molecular function of VAT-1. The amino acid sequence indicates that VAT-1 belongs to the quinone oxidoreductase subfamily, suggesting that VAT-1 may possess enzymatic activity in unknown redox processes. To clarify the molecular function of VAT-1, we determined the three-dimensional structure of human VAT-1 in the free state at 2.3 Å resolution and found that VAT-1 forms a dimer with the conserved NADPH-binding cleft on each protomer. We also determined the structure of VAT-1 in the NADP-bound state at 2.6 Å resolution and found that NADP binds the binding cleft to create a putative active site with the nicotine ring. Substrate screening suggested that VAT-1 possesses oxidoreductase activity against quinones such as 1,2-naphthoquinone and 9,10-phenanthrenequinone.https://doi.org/10.1038/s41598-021-81409-y |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sun-Yong Kim Tomoyuki Mori Min Fey Chek Shunji Furuya Ken Matsumoto Taisei Yajima Toshihiko Ogura Toshio Hakoshima |
spellingShingle |
Sun-Yong Kim Tomoyuki Mori Min Fey Chek Shunji Furuya Ken Matsumoto Taisei Yajima Toshihiko Ogura Toshio Hakoshima Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family Scientific Reports |
author_facet |
Sun-Yong Kim Tomoyuki Mori Min Fey Chek Shunji Furuya Ken Matsumoto Taisei Yajima Toshihiko Ogura Toshio Hakoshima |
author_sort |
Sun-Yong Kim |
title |
Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family |
title_short |
Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family |
title_full |
Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family |
title_fullStr |
Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family |
title_full_unstemmed |
Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family |
title_sort |
structural insights into vesicle amine transport-1 (vat-1) as a member of the nadph-dependent quinone oxidoreductase family |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-01-01 |
description |
Abstract Vesicle amine transport protein-1 (VAT-1) has been implicated in the regulation of vesicular transport, mitochondrial fusion, phospholipid transport and cell migration, and is a potential target of anticancer drugs. Little is known about the molecular function of VAT-1. The amino acid sequence indicates that VAT-1 belongs to the quinone oxidoreductase subfamily, suggesting that VAT-1 may possess enzymatic activity in unknown redox processes. To clarify the molecular function of VAT-1, we determined the three-dimensional structure of human VAT-1 in the free state at 2.3 Å resolution and found that VAT-1 forms a dimer with the conserved NADPH-binding cleft on each protomer. We also determined the structure of VAT-1 in the NADP-bound state at 2.6 Å resolution and found that NADP binds the binding cleft to create a putative active site with the nicotine ring. Substrate screening suggested that VAT-1 possesses oxidoreductase activity against quinones such as 1,2-naphthoquinone and 9,10-phenanthrenequinone. |
url |
https://doi.org/10.1038/s41598-021-81409-y |
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