Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis
oleh: Elizabeth R. Morris, Sarah J. Caswell, Simone Kunzelmann, Laurence H. Arnold, Andrew G. Purkiss, Geoff Kelly, Ian A. Taylor
| Format: | Article |
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| Diterbitkan: | Nature Portfolio 2020-06-01 |
Deskripsi
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.