Beilstein J. Org. Chem.2019,15, 145–159, doi:10.3762/bjoc.15.15
is an unusual cofactor in that, even without the enzyme, it can catalyze many of these reactions [2]. For example, the decarboxylation of pyruvate in water can be accomplished by ThDP, but when it is bound to the enzyme pyruvatedecarboxylase (PDC), the decarboxylation rate is increased by 12 orders
for the APH+ form. However, solid-state NMR using 15N and 13C-labeled ThDP has been used to identify APH+ on pyruvatedecarboxylase and the E1 component of the pyruvate dehydrogenase complex [18].
In addition to the plethora of experimental investigations, a number of computational studies have
, computational studies have been used to investigate full reaction mechanisms of ThDP enzymes, including pyruvatedecarboxylase (PDC) [25][26][27][28], benzoylformate decarboxylase (BFDC) [29][30], acetohydroxy acid synthase [24][31][32][33][34][35], pyruvate dehydrogenase (PDH) [36], benzaldehyde lyase [37
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Graphical Abstract
Scheme 1:
The variety of forms of enzyme-bound ThDP.
Beilstein J. Org. Chem.2014,10, 2580–2585, doi:10.3762/bjoc.10.270
, involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvatedecarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a
; pyruvatedecarboxylase; thiamine diphosphate; Introduction
The biologically active form of vitamin B1 is thiamine diphosphate (ThDP, 1, Figure 1), which is an essential cofactor and involved in a number of metabolic pathways, including oxidative and non-oxidative decarboxylation of α-keto acids (e.g
., pyruvate dehydrogenase, pyruvatedecarboxylase), the formation of amino acid precursors (acetohydroxy acid synthase), and ketol transfer between sugars (transketolase) [1]. One common feature of ThDP-dependent enzymes is to catalyse the cleavage and formation of bonds adjacent to the carbon of a carbonyl
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Graphical Abstract
Figure 1:
Structure of thiamine diphosphate (ThDP, 1).