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

It is theoretically plausible that thiazolium mesomerizes to congeners other than carbene in a low effective dielectric binding site; especially given the energetics and uneven electronegativity of carbene groups. However, such a phenomenon has never been reported. Nine crystal structures of transke...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-02, Vol.57 (7), p.1802-1807
Main Authors: Hsu, Ning‐Shian, Wang, Yung‐Lin, Lin, Kuan‐Hung, Chang, Chi‐Fon, Lyu, Syue‐Yi, Hsu, Li‐Jen, Liu, Yu‐Chen, Chang, Chin‐Yuan, Wu, Chang‐Jer, Li, Tsung‐Lin
Format: Article
Language:English
Subjects:
Binding sites
Congeners
Crystal structure
Dehydration
Electronegativity
non-Kekulé diradicals
Pichia
Pichia stipitis
Substrates
Thiamine
thiamine diphosphate
thiazolium
Transketolase
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Summary:It is theoretically plausible that thiazolium mesomerizes to congeners other than carbene in a low effective dielectric binding site; especially given the energetics and uneven electronegativity of carbene groups. However, such a phenomenon 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‐Kekulé diradicals because there is no gain or loss of electrons. In conjunction with biophysical and biochemical analyses, it is concluded that ring bending is a result of tautomerization of thiazolium with its non‐ Kekulé diradicals, exclusively in the binding site of TKps. The chemophysical properties of these thiazolium mesomers may account for the great variety of reactivities carried out by thiamine–diphosphate‐containing (ThDP) enzymes. The 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. The aromaticity of thiazolium is considered essential for the structural integrity of the cofactor and catalytic efficacy of thiamine–diphosphate‐containing enzymes. A thiazolium bending effect has been observed, which accounts for the great variety of reactivities carried out by these enzymes and may be applicable to metabolism of the cofactor in living organisms.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201709799