title: [Thymidylate synthase-catalyzed reaction mechanism].
abstract: Thymidylate synthase ThyA (EC 2.1.1.45;-encoded by the Tyms gene), having been for 60 years a molecular target in chemotherapy, catalyses the dUMP pyrimidine ring C(5) methylation reaction, encompassing a transfer of one-carbon group (the methylene one, thus at the formaldehyde oxidation level) from 6R-N5,10-methylenetetrahydrofolate, coupled with a reduction of this group to the methyl one, with concomitant generation of 7,8-dihydrofolate and thymidylate. New facts are presented, concerning (i) molecular mechanism of the catalyzed reaction, including the substrate selectivity mechanism, (ii) mechanism of inhibition by a particular inhibitor, N4-hydroxy-dCMP, (iii) structural properties of the enzyme, (iv) cellular localization, (v) potential posttranslational modifications of the enzyme protein and their influence on the catalytic properties and (vi) non-catalytic activities of the enzyme.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rode
authors.forename: Adam
authors.initials: A
authors.lastname: Jarmuńa
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000266:history*; D004791:Enzyme Inhibitors / Q000266:history / Q000494:pharmacology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007700:Kinetics; D011044:Poland; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000266:history* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013940:Thymidylate Synthase