CHEM 313 Chapter Notes -Thiazole, Pyrimidine, Protonation
Document Summary
Chem 313 problem set #9, 2014, answers: answer in scheme below, answer in the scheme below, annual rev. 2009, 78, 569:thiamin is positioned in the active site by two hydrogen bonds between the pyrimidine moiety and asp272, one of which occurs through an intervening water molecule. Glu241 then activates cys113 for attack at c-6 of the pyrimidine to form a zwitterionic intermediate. Nucleophilic attack and protonation by glu241 result in cleavage of the bond between the thiazole and pyrimidine and release of products: j. 2007, 129, 4120: researchers hypothesized that, as shown in. Scheme 2, (4) would undergo nucleophilic attack by the ylid of thdp to provide the adduct, (5). However, unlike (3), (5) has an anion-stabilizing phenyl group. This gives (5) the potential for a more facile elimination of metaphosphate which might lead to enzyme phosphorylation and, concomitantly, irreversible inhibition.
