Spratt, Thomas E.; De los Santos, Hannah published the artcile< Reaction of O6-alkylguanine-DNA alkyltransferase with O6-methylguanine analogs: evidence that the oxygen of O6-methylguanine is protonated by the protein to effect methyl transfer>, Application In Synthesis of 84955-32-8, the main research area is alkylguanine DNA alkyltransferase methylguanine analog.
The DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) repairs the promutagenic O6-methylguanine lesion by transferring the Me group to a cysteine residue on the protein. A mechanism in which AGT activates the guanyl moiety as a leaving group by protonation of a heteroatom on guanine was probed by reacting AGT with analogs of O6-methylguanine in which the heteroatoms were changed. The initial rates of reaction were measured at various substrate concentrations in 50 mM Hepes, 1 mM EDTA, 1 mM DTT, and 10% glycerol, pH 7.8 at 37). The kinact (h-1) and Kin (mM) were determined for O6-methylguanine (1.66, 1.51) 0.32), 6-methoxypurine (1.07, 10.6), S6-methyl-6-thioguanine (0.63, 1.17), 6-methylthiopurine (no reaction), Se6-methyl-6-selenoguanine (1.76, 10.6), 6-methylselenopurine (2.51, 15.7), O6-methyl-1-deazaguanine (1.71, 14.8), O6-methyl-3-deazaguanine (1.90, 2.54), and O6-methyl-7-deazaguanine (1.97, 2.56). These results indicate that replacement of the nitrogens does not affect the kinact parameter but the Kin is increased upon removal of the exocyclic amino group and the nitrogen at the 1-position. Replacement of the oxygen with sulfur decreases the kinact, and replacement with selenium increases the Kin. The results are consistent with a mechanism in which O6-methylguanine binds to the active site of AGT with hydrogen bonds to the oxygen, the exocyclic amino group, and the nitrogen at the 1-position of the substrate. The Me group is then displaced from the guanine as a proton is transferred to the oxygen, neutralizing the charge on the leaving group.
Biochemistry published new progress about 84955-32-8. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Application In Synthesis of 84955-32-8.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia