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CoFactor: Thiamine diphosphate

General information

2D representation

Thiamine diphosphate

Key facts

Cofactor type    prosthetic group
Human metabolism    Vitamin B1
IUPAC name    2-{3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl}ethyl dihydrogen diphosphate
Curator    JDF

Tags

Molecular function

ThDP catalyses the formation and cleavage of C-S, C-N, C-O and the chemically challenging C-C bonds using the enamine intermediate carbanion. [1]

Chemical properties

Thiamine diphosphate (ThDP) consists of three parts:
  1. a 6-membered aminopyrimidine ring
  2. a 5-membered thiazolium ring, which includes the catalytic C2 atom
  3. diphosphate.
ThDP builds an imino-intermediate by tautomerisation. nucleophilic attack of a COO- group at the NH2 group of the pyrimidine ring leads to the formation of a carbanion at C2. [1]

The sequence motif for the ThDP binding site is GDG(X)N and binds the diphosphate group, which is usually coordinated by a Mg2+ ion. The aminopyrimidine ring binds in a hydrophobic pocket, in proximity to an activating invariant GLU residue. Accessibility to the active site is varying and depends on the length of active site loops. [1]

Pathways

Thiamine diphosphate metabolism is shared by all forms of life[2]. TPP is involved in energy production, sugar metabolism and other essential pathways [6].

Comment

The deficiency disease of ThDP in humans is called beri-beri. [6]

References

[1] pubmed:17429582
[2] pubmed:18183975
[3] pubmed:20739284
[4] pubmed:20956531
[5] pubmed:17898894
[6] pubmed:17898888
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