On December 31, 2000, Petronzelli, Fiorella; Riccio, Antonio; Markham, George D.; Seeholzer, Steven H.; Genuardi, Maurizio; Karbowski, Mariola; Yeung, Anthony T.; Matsumoto, Yoshihiro; Bellacosa, Alfonso published an article.Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was Investigation of the substrate spectrum of the human mismatch-specific DNA N-glycosylase MED1 (MBD4): fundamental role of the catalytic domain. And the article contained the following:
The human DNA repair protein MED1 (also known as MBD4) was isolated as an interactor of the mismatch repair protein MLH1 in a yeast two-hybrid screening. MED1 has a tripartite structure with an N-terminal 5-methylcytosine binding domain (MBD), a central region, and a C-terminal catalytic domain with homol. to bacterial DNA damage-specific glycosylases/lyases. Indeed, MED1 acts as a mismatch-specific DNA N-glycosylase active on thymine, uracil, and 5-fluorouracil paired with guanine. The glycosylase activity of MED1 preferentially targets G:T mismatches in the context of CpG sites; this indicates that MED1 is involved in the repair of deaminated 5-methylcytosine. Interestingly, frameshift mutations of the MED1 gene have been reported in human colorectal, endometrial, and pancreatic cancers. For its putative role in maintaining genomic fidelity at CpG sites, it is important to characterize the biochem. properties and the substrate spectrum of MED1. Here we show that MED1 works under a wide range of temperature and pH, and has a limited optimum range of ionic strength. MED1 has a weak glycosylase activity on the mutagenic adduct 3,N4-ethenocytosine, a metabolite of vinyl chloride and Et carbamate. The differences in glycosylase activity on G:U and G:T substrates are not related to differences in substrate binding and likely result from intrinsic differences in the chem. step. Finally, the isolated catalytic domain of MED1 retains the preference for G:T and G:U substrates in the context of methylated or unmethylated CpG sites. This suggests that the catalytic domain is fundamental, and the 5-methylcytosine binding domain dispensable, in determining the substrate spectrum of MED1. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one
The Article related to dna glycosylase med1 catalytic domain substrate specificity, mbd4 dna glycosylase catalytic domain substrate specificity, Enzymes: Structure-Conformation-Active Site and other aspects.Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one
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Imidazole | C3H4N2 – PubChem