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Literature summary for 3.1.5.B1 extracted from

  • 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, X.
    Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase (2013), Nat. Commun., 4, 2722.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
dGTP allosteric activator. Allosteric dGTP binding induces conformational changes at the active site, allowing a more stable interaction with the substrate and explaining the dGTP-induced isoform SAMHD1 dNTPase activity. Mutations of dGTP binding residues in the allosteric site affect tetramer formation, dNTPase activity and HIV-1 restriction Homo sapiens
additional information dGTP, but not the other dNTPs, is required for the formation and maintenance of the catalytically more active SAMHD1 tetramer Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
in complex with the allosteric activator and substrate dGTP/dATP, to 1.8 A resolution Homo sapiens

Protein Variants

Protein Variants Comment Organism
D137A reduced ability to form tetramers, reduced dNTPase activity Homo sapiens
Q142E/R145K reduced ability to form tetramers, reduced dNTPase activity Homo sapiens
R333E reduced ability to form tetramers, reduced dNTPase activity Homo sapiens
R333E/R451E reduced ability to form tetramers, reduced dNTPase activity Homo sapiens
R451E reduced ability to form tetramers, reduced dNTPase activity Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
72000
-
and 280000, gel filtration Homo sapiens
72600
-
1 * 72600, and tetramer, 4 * 72600, analytical ultracentrifugation. Formation of tetramer is induced by dGTP, tetramer is a more potent dNTPase than monomer Homo sapiens
72600
-
4 * 72600, and monomer, 1 * 72600, analytical ultracentrifugation. Formation of tetramer is induced by dGTP, tetramer is a more potent dNTPase than monomer Homo sapiens
280000
-
and 72000, gel filtration Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
dATP + H2O
-
Homo sapiens deoxyadenosine + triphosphate
-
?
dGTP + H2O
-
Homo sapiens deoxyguanosine + triphosphate
-
?

Subunits

Subunits Comment Organism
monomer 1 * 72600, and tetramer, 4 * 72600, analytical ultracentrifugation. Formation of tetramer is induced by dGTP, tetramer is a more potent dNTPase than monomer Homo sapiens
tetramer 4 * 72600, and monomer, 1 * 72600, analytical ultracentrifugation. Formation of tetramer is induced by dGTP, tetramer is a more potent dNTPase than monomer Homo sapiens

Synonyms

Synonyms Comment Organism
deoxynucleoside triphosphate triphosphohydrolase
-
Homo sapiens
SAMHD1
-
Homo sapiens

General Information

General Information Comment Organism
physiological function allosteric dGTP binding induces conformational changes at the active site, allowing a more stable interaction with the substrate and explaining the dGTP-induced dNTPase activity. Mutations of dGTP binding residues in the allosteric site affect tetramer formation, dNTPase activity and HIV-1 restriction. dGTP-triggered tetramer formation is also important for SAMHD1-mediated retrotransposition of LINE-1 elements Homo sapiens