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
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Acceso en línea:https://doaj.org/article/33c0aeb332314b7f823450d37d5ea349
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Sumario: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.