title: Mechanistic studies of the radical S-adenosylmethionine enzyme DesII with TDP-D-fucose.
abstract: DesII is a radical S-adenosylmethionine (SAM) enzyme that catalyzes the C4-deamination of TDP-4-amino-4,6-dideoxyglucose through a C3 radical intermediate. However, if the C4 amino group is replaced with a hydroxy group (to give TDP-quinovose), the hydroxy group at C3 is oxidized to a ketone with no C4-dehydration. It is hypothesized that hyperconjugation between the C4 C-N/O bond and the partially filled p orbital at C3 of the radical intermediate modulates the degree to which elimination competes with dehydrogenation. To investigate this hypothesis, the reaction of DesII with the C4-epimer of TDP-quinovose (TDP-fucose) was examined. The reaction primarily results in the formation of TDP-6-deoxygulose and likely regeneration of TDP-fucose. The remainder of the substrate radical partitions roughly equally between C3-dehydrogenation and C4-dehydration. Thus, changing the stereochemistry at C4 permits a more balanced competition between elimination and dehydrogenation.
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry, University of Texas at Austin, Austin, TX 78712 (USA).
authors.forename: Yeonjin
authors.initials: Y
authors.lastname: Ko
authors.forename: Mark W
authors.initials: MW
authors.lastname: Ruszczycky
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Choi
authors.forename: Hung-wen
authors.initials: HW
authors.lastname: Liu
mesh_terms: D055162:Biocatalysis; D020134:Catalytic Domain; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism*; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013302:Streptomyces / Q000201:enzymology; D013379:Substrate Specificity; D013942:Thymine Nucleotides / Q000378:metabolism*
chemical_list: D005609:Free Radicals; D009702:Nucleoside Diphosphate Sugars; D013942:Thymine Nucleotides; C119709:thymidine diphosphate fucose; D006867:Hydrolases; C019614:adenosylmethionine hydrolase
keywords: S-adenosylmethionine; biosynthesis; carbohydrates; enzyme catalysis; radical reactions