Thymidyl biosynthesis enzymes as antibiotic targets.
The two long-known "classical" enzymes of uridyl-5-methylation, thymidylate synthase and ribothymidyl synthase, have been joined by two alternative methylation enzymes, flavin-dependent thymidylate synthase and folate-dependent ribothymidyl synthase. These two newly discovered enzymes have much in common: both contain flavin cofactors, utilize methylenetetrahydrofolate as a source of methyl group, and perform thymidylate synthesis via chemical pathways distinct from those of their classic counterparts. Several severe human pathogens (e.g., typhus, anthrax, tuberculosis, and more) depend on these "alternative" enzymes for reproduction. These and other distinctive properties make the alternative enzymes and their corresponding genes appealing targets for new antibiotics.
Chernyshev
Anatoly
A
Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Fleischmann
Todd
T
Kohen
Amnon
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005415:Flavins / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013936:Thymidine / Q000096:biosynthesis*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005415:Flavins; D005492:Folic Acid; D008780:Methyltransferases; C024841:ribothymidyl synthase; D013940:Thymidylate Synthase; D013936:Thymidine