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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Autores principales:	Sun-Yong Kim, Tomoyuki Mori, Min Fey Chek, Shunji Furuya, Ken Matsumoto, Taisei Yajima, Toshihiko Ogura, Toshio Hakoshima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/243aedf7faa34e3f9c181105aa9c440f
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spelling	oai:doaj.org-article:243aedf7faa34e3f9c181105aa9c440f2021-12-02T10:49:16ZStructural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family10.1038/s41598-021-81409-y2045-2322https://doaj.org/article/243aedf7faa34e3f9c181105aa9c440f2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81409-yhttps://doaj.org/toc/2045-2322Abstract 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.Sun-Yong KimTomoyuki MoriMin Fey ChekShunji FuruyaKen MatsumotoTaisei YajimaToshihiko OguraToshio HakoshimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Sun-Yong Kim Tomoyuki Mori Min Fey Chek Shunji Furuya Ken Matsumoto Taisei Yajima Toshihiko Ogura Toshio Hakoshima
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 Portfolio
publishDate	2021
url	https://doaj.org/article/243aedf7faa34e3f9c181105aa9c440f
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Structural insights into vesicle amine transport-1 (VAT-1) as a member of the NADPH-dependent quinone oxidoreductase family

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