title: Activation and inhibition of DNA methyltransferases by S-adenosyl-L-homocysteine analogues.
abstract: The inhibition of methyltransferases is currently of high interest, particularly in the areas of microbial infection and cell proliferation, as there have been serious attempts to develop novel anti-microbial agents. In the present investigation, a series of 11 S-adenosyl-l-homocysteine analogues have been synthesized and effect of these analogues on DNA methylation catalyzed by DNA methyltransferases was studied. It was found that, while 5'-S-(propionic acid)5'-deoxy-9-(1'-beta-d-ribofuranosyl)1,3-dideazaadenine was an activator of EcoP15I and HhaI DNA methyltransferases, 5'-S-(propionic acid)5'-deoxy-9-(1'-beta-dribofuranosyl)adenine inhibited the methyltransferases in a non-competitive manner. An understanding of the binding of analogues to DNA methyltransferases will greatly assist the design of novel anti-microbial compounds.
authors: Department of Biochemistry, Indian Institute of Science, Banglore 560012, India.
authors: Ritesh
authors: R
authors: Kumar
authors: Richa
authors: R
authors: Srivastava
authors: Ramendra Kumar
authors: RK
authors: Singh
authors: Avadhesha
authors: A
authors: Surolia
authors: Desirazu N
authors: DN
authors: Rao
mesh_terms: D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D015394:Molecular Structure; D012435:S-Adenosylhomocysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012706:Serratia marcescens / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D012435:S-Adenosylhomocysteine; D015254:DNA Modification Methylases