The shape of human squalene epoxidase expands the arsenal against cancer

Abstract Squalene epoxidase (also known as squalene monooxygenase, EC 1.14.99.7) is a key rate-limiting enzyme in cholesterol biosynthesis. Anil Padyana and colleagues report the long awaited structure of human squalene epoxidase (SQLE). They solved the crystal structure of the catalytic domain of h...

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Autores principales:	Andrew J. Brown, Ngee Kiat Chua, Nieng Yan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/aef4b715043743b3a89265bef8cffcc9
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spelling	oai:doaj.org-article:aef4b715043743b3a89265bef8cffcc92021-12-02T16:57:41ZThe shape of human squalene epoxidase expands the arsenal against cancer10.1038/s41467-019-08866-y2041-1723https://doaj.org/article/aef4b715043743b3a89265bef8cffcc92019-02-01T00:00:00Zhttps://doi.org/10.1038/s41467-019-08866-yhttps://doaj.org/toc/2041-1723Abstract Squalene epoxidase (also known as squalene monooxygenase, EC 1.14.99.7) is a key rate-limiting enzyme in cholesterol biosynthesis. Anil Padyana and colleagues report the long awaited structure of human squalene epoxidase (SQLE). They solved the crystal structure of the catalytic domain of human SQLE alone and in complex with two similar pharmacological inhibitors and elucidate their mechanism of action. SQLE is the target of fungicides and of increasing interest in human health and disease, particularly as a new anti-cancer target. Indeed, in a companion paper, Christopher Mahoney and colleagues performed an inhibitor screen with cancer cell lines and identified SQLE as an unique vulnerability in a subset of neuroendocrine tumours, where SQLE inhibition caused a toxic accumulation of the substrate squalene. The SQLE structure will facilitate the development of improved inhibitors. Here, we comment on these two studies in the wider context of the field and discuss possible future directions.Andrew J. BrownNgee Kiat ChuaNieng YanNature PortfolioarticleScienceQENNature Communications, Vol 10, Iss 1, Pp 1-4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Andrew J. Brown Ngee Kiat Chua Nieng Yan The shape of human squalene epoxidase expands the arsenal against cancer
description	Abstract Squalene epoxidase (also known as squalene monooxygenase, EC 1.14.99.7) is a key rate-limiting enzyme in cholesterol biosynthesis. Anil Padyana and colleagues report the long awaited structure of human squalene epoxidase (SQLE). They solved the crystal structure of the catalytic domain of human SQLE alone and in complex with two similar pharmacological inhibitors and elucidate their mechanism of action. SQLE is the target of fungicides and of increasing interest in human health and disease, particularly as a new anti-cancer target. Indeed, in a companion paper, Christopher Mahoney and colleagues performed an inhibitor screen with cancer cell lines and identified SQLE as an unique vulnerability in a subset of neuroendocrine tumours, where SQLE inhibition caused a toxic accumulation of the substrate squalene. The SQLE structure will facilitate the development of improved inhibitors. Here, we comment on these two studies in the wider context of the field and discuss possible future directions.
format	article
author	Andrew J. Brown Ngee Kiat Chua Nieng Yan
author_facet	Andrew J. Brown Ngee Kiat Chua Nieng Yan
author_sort	Andrew J. Brown
title	The shape of human squalene epoxidase expands the arsenal against cancer
title_short	The shape of human squalene epoxidase expands the arsenal against cancer
title_full	The shape of human squalene epoxidase expands the arsenal against cancer
title_fullStr	The shape of human squalene epoxidase expands the arsenal against cancer
title_full_unstemmed	The shape of human squalene epoxidase expands the arsenal against cancer
title_sort	shape of human squalene epoxidase expands the arsenal against cancer
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/aef4b715043743b3a89265bef8cffcc9
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The shape of human squalene epoxidase expands the arsenal against cancer

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