Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis

SAMHD1 catalyses the hydrolysis of dNTPs into 2′-deoxynucleosides and triphosphate and is an important regulator of cellular dNTP homeostasis. Here, the authors provide insights into the catalytic mechanism of SAMHD1 by performing kinetic measurements and determining crystal structures of α-β-imido-...

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Autores principales:	Elizabeth R. Morris, Sarah J. Caswell, Simone Kunzelmann, Laurence H. Arnold, Andrew G. Purkiss, Geoff Kelly, Ian A. Taylor
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/33c0aeb332314b7f823450d37d5ea349
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spelling	oai:doaj.org-article:33c0aeb332314b7f823450d37d5ea3492021-12-02T17:45:10ZCrystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis10.1038/s41467-020-16983-22041-1723https://doaj.org/article/33c0aeb332314b7f823450d37d5ea3492020-06-01T00:00:00Zhttps://doi.org/10.1038/s41467-020-16983-2https://doaj.org/toc/2041-1723SAMHD1 catalyses the hydrolysis of dNTPs into 2′-deoxynucleosides and triphosphate and is an important regulator of cellular dNTP homeostasis. Here, the authors provide insights into the catalytic mechanism of SAMHD1 by performing kinetic measurements and determining crystal structures of α-β-imido-dNTP inhibitor complexes, which reveal a bi-metallic iron-magnesium centre and catalytic hydroxyl molecule in the active site of the enzyme.Elizabeth R. MorrisSarah J. CaswellSimone KunzelmannLaurence H. ArnoldAndrew G. PurkissGeoff KellyIan A. TaylorNature PortfolioarticleScienceQENNature Communications, Vol 11, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Elizabeth R. Morris Sarah J. Caswell Simone Kunzelmann Laurence H. Arnold Andrew G. Purkiss Geoff Kelly Ian A. Taylor Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
description	SAMHD1 catalyses the hydrolysis of dNTPs into 2′-deoxynucleosides and triphosphate and is an important regulator of cellular dNTP homeostasis. Here, the authors provide insights into the catalytic mechanism of SAMHD1 by performing kinetic measurements and determining crystal structures of α-β-imido-dNTP inhibitor complexes, which reveal a bi-metallic iron-magnesium centre and catalytic hydroxyl molecule in the active site of the enzyme.
format	article
author	Elizabeth R. Morris Sarah J. Caswell Simone Kunzelmann Laurence H. Arnold Andrew G. Purkiss Geoff Kelly Ian A. Taylor
author_facet	Elizabeth R. Morris Sarah J. Caswell Simone Kunzelmann Laurence H. Arnold Andrew G. Purkiss Geoff Kelly Ian A. Taylor
author_sort	Elizabeth R. Morris
title	Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
title_short	Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
title_full	Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
title_fullStr	Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
title_full_unstemmed	Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
title_sort	crystal structures of samhd1 inhibitor complexes reveal the mechanism of water-mediated dntp hydrolysis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/33c0aeb332314b7f823450d37d5ea349
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_version_	1718379578604388352

Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis

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