SAMHD1:Zn2+ tetramer hydrolyzes dNTP to nucleoside and triphosphate

Stable Identifier
R-HSA-8866601
Type
Reaction [transition]
Species
Homo sapiens
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SAMHD1:Zn2+ tetramer (Deoxynucleoside triphosphate triphosphohydrolase SAMHD1, also known as SAM domain and HD domain-containing protein 1) catalyzes the hydrolysis of dNTPs (2'-deoxynucleoside 5'-triphosphates) to form 2'-deoxynucleosides and PPPi (triphosphate) (Goldstone et al. 2011; Powell et al. 2011). The active form of the enzyme is a tetramer with one Zn2+ ion associated with each monomer subunit (Yan et al. 2013; Zhu et al. 2013) localized in the nucleus (Franzolin et al. 2013; Rice et al. 2009). The enzyme is activated by dGTP (Powell et al. 2011).

SAMHD1 activity may play a role in regulating the size of the nuclear pools of dNTPs and dissipating these pools at the end of the S phase of the cell cycle (Franzolin et al. 2013) and it may play a role as well in regulating cellular antiviral responses (Goldstone et al. 2011; Rice et al. 2009).

Literature References
PubMed ID Title Journal Year
24217394 Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase

Zhu, C, Gao, W, Zhao, K, Qin, X, Zhang, Y, Peng, X, Zhang, L, Dong, Y, Zhang, W, Li, P, Wei, W, Gong, Y, Yu, XF

Nat Commun 2013
22056990 HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase

Goldstone, DC, Ennis-Adeniran, V, Hedden, JJ, Groom, HC, Rice, GI, Christodoulou, E, Walker, PA, Kelly, G, Haire, LF, Yap, MW, de Carvalho, LP, Stoye, JP, Crow, YJ, Taylor, IA, Webb, M

Nature 2011
22069334 Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase

Powell, RD, Holland, PJ, Hollis, T, Perrino, FW

J. Biol. Chem. 2011
19525956 Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

Rice, GI, Bond, J, Asipu, A, Brunette, RL, Manfield, IW, Carr, IM, Fuller, JC, Jackson, RM, Lamb, T, Briggs, TA, Ali, M, Gornall, H, Couthard, LR, Aeby, A, Attard-Montalto, SP, Bertini, E, Bodemer, C, Brockmann, K, Brueton, LA, Corry, PC, Desguerre, I, Fazzi, E, Cazorla, AG, Gener, B, Hamel, BC, Heiberg, A, Hunter, M, van der Knaap, MS, Kumar, R, Lagae, L, Landrieu, PG, Lourenco, CM, Marom, D, McDermott, MF, van der Merwe, W, Orcesi, S, Prendiville, JS, Rasmussen, M, Shalev, SA, Soler, DM, Shinawi, M, Spiegel, R, Tan, TY, Vanderver, A, Wakeling, EL, Wassmer, E, Whittaker, E, Lebon, P, Stetson, DB, Bonthron, DT, Crow, YJ

Nat. Genet. 2009
23858451 The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA precursor pools in mammalian cells

Franzolin, E, Pontarin, G, Rampazzo, C, Miazzi, C, Ferraro, P, Palumbo, E, Reichard, PA, Bianchi, V

Proc. Natl. Acad. Sci. U.S.A. 2013
23426366 Tetramerization of SAMHD1 is required for biological activity and inhibition of HIV infection

Yan, J, Kaur, S, DeLucia, M, Hao, C, Mehrens, J, Wang, C, Golczak, M, Palczewski, K, Gronenborn, AM, Ahn, J, Skowronski, J

J. Biol. Chem. 2013
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Catalyst Activity
Title
triphosphoric monoester hydrolase activity of SAMHD1:Zn2+ tetramer [nucleoplasm]
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