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SET and RING-finger-associated (SRA) domain is involved in establishment and maintenance of DNA methylation in eukaryotes. Proteins containing SRA domains exist in mammals, plants, even microorganisms. It has been established that mammalian SRA domain recognizes 5-methylcytosine (5mC) through a base-flipping mechanism. Here, we identified and characterized(More)
DNA phosphorothioation (PT) is the first discovered physiological DNA backbone modification, in which a non-bridging oxygen atom of the phosphodiester bond is replaced with a sulfur atom in Rp (rectus for plane) configuration. PT modification is governed by a highly conserved gene cluster dndA/iscS-dndBCDE that is widespread across bacterial and archaeal(More)
5-Hydroxymethylcytosine (5hmC) is present in T-even phage and mammalian DNA as well as some nucleoside antibiotics, including mildiomycin and bacimethrin, during whose synthesis 5hmC is produced by the hydrolysis of 5-hydroxymethyl cytidine 5'-monophosphate (hmCMP) by an N-glycosidase MilB. Recently, the MilB-CMP complex structure revealed its substrate(More)
Modified pyrimidine monophosphates such as methyl dCMP (mdCMP), hydroxymethyl dUMP (hmdUMP) and hmdCMP in some phages are synthesized by a large group of enzymes termed as thymidylate synthases (TS). Thymidylate is a nucleotide required for DNA synthesis and thus TS is an important drug target. In the biosynthetic pathway of the nucleoside fungicide(More)
The role of nitric oxide (NO) in the regulation of 02 consumption was studied in chronically instrumented conscious dogs. A specific NO synthesis inhibitor, nitro-L-arginine (NLA, 30 mg/kg IV), significantly increased mean arterial pressure from 100±4 to 134±5 mm Hg (mean±SEM) and total peripheral resistance by 157±16% and reduced cardiac output by 47±3%(More)
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