title: Mechanisms and inhibition of uracil methylating enzymes.
abstract: Uracil methylation is essential for survival of organisms and passage of information from generation to generation with high fidelity. Two alternative uridyl methylation enzymes, flavin-dependent thymidylate synthase and folate/FAD-dependent RNA methyltransferase, have joined the long-known classical enzymes, thymidylate synthase and SAM-dependent RNA methyltransferase. These alternative enzymes differ significantly from their classical counterparts in structure, cofactor requirements and chemical mechanism. This review covers the available structural and mechanistic knowledge of the classical and alternative enzymes in biological uracil methylation, and offers a possibility of using inhibitors specifically aiming at microbial thymidylate production as antimicrobial drugs.
authors.affiliation: Department of Chemistry, The University of Iowa, E274 Chemistry Building, Iowa City, IA 52245, USA.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Mishanina
authors.forename: Eric M
authors.initials: EM
authors.lastname: Koehn
authors.forename: Amnon
authors.initials: A
authors.lastname: Kohen
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism; D055162:Biocatalysis; D004926:Escherichia coli / Q000201:enzymology; D005415:Flavins / Q000378:metabolism; D008745:Methylation; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014498:Uracil / Q000378:metabolism*; D012359:tRNA Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D005415:Flavins; D014498:Uracil; D012359:tRNA Methyltransferases; D013940:Thymidylate Synthase