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Mechanistic Studies of the Radical S ‐Adenosylmethionine Enzyme DesII with TDP‐ D ‐Fucose
Author(s) -
Ko Yeonjin,
Ruszczycky Mark W.,
Choi SeiHyun,
Liu Hungwen
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201409540
Subject(s) - chemistry , dehydrogenation , deamination , fucose , stereochemistry , substrate (aquarium) , decarboxylation , medicinal chemistry , epimer , enzyme , dehydration , biochemistry , catalysis , oceanography , geology , glycoprotein
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 CN/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.