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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Main Authors: Sun-Yong Kim, Tomoyuki Mori, Min Fey Chek, Shunji Furuya, Ken Matsumoto, Taisei Yajima, Toshihiko Ogura, Toshio Hakoshima
Format: Article
Language:English
Published: Nature Publishing Group 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-81409-y
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spelling 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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