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Literature summary for 3.1.5.B1 extracted from

  • Jang, S.; Zhou, X.; Ahn, J.
    Substrate specificity of SAMHD1 triphosphohydrolase activity is controlled by deoxyribonucleoside triphosphates and phosphorylation at Thr592 (2016), Biochemistry, 55, 5635-5646 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
T592D mutant as well as phospho-Thr592, show a significantly altered substrate specificity, with the rate of dCTP hydrolysis being selectively reduced regardless of which dNTP binds at allosteric site AS2 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0016
-
dATP dCTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0016
-
dCTP dCTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.002
-
dTTP dCTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0021
-
dGTP dCTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0028
-
dATP dGTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0033
-
dCTP dGTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0035
-
dTTP dGTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0037
-
dGTP dGTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0041
-
dATP dATP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0056
-
dCTP dATP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0065
-
dGTP dATP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0077
-
dTTP dATP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0135
-
dGTP dTTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0142
-
dATP dTTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0153
-
dTTP dTTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication Homo sapiens
0.0225
-
dCTP dTTP bound at allosteric site AS2, pH 7.8, temperature not specified in the publication 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 deoxyadeonsine + triphosphate
-
?
dCTP + H2O
-
Homo sapiens deoxycytidine + triphosphate
-
?
dGTP + H2O
-
Homo sapiens deoxyguanosine + triphosphate
-
?
dTTP + H2O
-
Homo sapiens deoxythymidine + triphosphate
-
?

General Information

General Information Comment Organism
physiological function the monomer and apo- or GTP-bound dimer of SAMHD1 are catalytically inactive. Binding of dNTP at allosteric site 2 (AS2), adjacent to the GTP-binding, allosteric site 1 (AS1), induces formation of tetramer, the catalytically active form. The apparent Km values of dNTPs at AS2 vary, in increasing order of dCTP, dGTP, dATP, dTTP. dCTP binding at AS2 significantly reduces the dCTP hydrolysis rate, which is restored to a rate comparable to that of other dNTPs upon dGTP, dATP or dTTP binding at AS2. Cyclin A2 binding at the C-terminus of SAMHD1 induces disassembly of the SAMHD1 tetramer, Homo sapiens