The Mesomeric Effect of Thiazolium on non‐Kekulé Diradicals in Pichia stipitis Transketolase

Abstract

It is theoretically plausible that thiazolium mesomerizes to congeners other than carbene in al ow effective dielectric binding site;e specially given the energetics and uneven electronegativity of carbene groups.H owever,s uch aphenomenon has never been reported. Nine crystal structures of transketolase obtained from Pichia stipitis (TKps) are reported with subatomic resolution, where thiazolium displays an extraordinary ring-bending effect. The bent thiazolium congeners correlate with non-KekulØ diradicals because there is no gain or loss of electrons.Inconjunction with biophysical and biochemical analyses,i ti sc oncluded that ring bending is ar esult of tautomerization of thiazolium with its non-KekulØ diradicals,e xclusively in the binding site of TKps. The chemophysical properties of these thiazoliumm esomers may account for the great variety of reactivities carried out by thiamine-diphosphate-containing (ThDP) enzymes.T he stability of ThDP in living systems can be regulated by the levels of substrates,and hydration and dehydration, as well as diradical-mediated oxidative degradation.