Proteopedia

Thiamin phosphate synthase

Function

Thiamin phosphate synthase (TPS) or thiamin-phosphate pyrophosphorylase catalyzes the synthesisd of 4-methyl-5 (β-hydroxyethyl)thiazole phosphate (Thz-P) amd 4-amino-5(hydroxymethyl)-2-methylpyrimidine pyrophosphate (HMP-PP) to produce thiamin phosphate and pyrophosphate[1].

Relevance

Thiamin is an essential component of human diet. Thiamin deficiency is associated with neurodegenerative diseases[2], delirium[3], obesity[4] and results in beriberi[5] and in the alcoholic brain disease Korsakoff's syndrome[6]. TPS is involved in thiamin biosynthesis.

Structural highlights

The . TPS reaction products thiamin phosphate and pyrophosphate interact with various residues of the protein as well as with each other[7].

  • .
  • . Water molecules are shown as red spheres.
  • .
  • .
  • .

3D structures of thiamin phosphate synthase

Updated on 04-May-2025

1g4e, 3o16 - BsTPS (mutant) - Bacillus subtilis

1g4p - BsTPS (mutant) + Thz-P
1g67, 1g69, 1g6c - BsTPS (mutant) + Thz-P + PPi
1g4t - BsTPS + thiamine phosphate derivative
1g4s - BsTPS (mutant) + thiamine phosphate derivative
2tps - BsTPS + thiamine phosphate + PPi
3o15 - BsTPS + thiazole phosphate derivative + PPi
3o63 - TPS + Pi - Mycobacterium tuberculosis
1xi3 - TPS - Pyrococcus furiosus
3ceu - TPS - Bacterioides thetaiotamicron

References

  1. ↑ Reddick JJ, Nicewonger R, Begley TP. Mechanistic studies on thiamin phosphate synthase: evidence for a dissociative mechanism. Biochemistry. 2001 Aug 28;40(34):10095-102. PMID:11513588
  2. ↑ Dumitrascu R, Koebrich S, Dony E, Weissmann N, Savai R, Pullamsetti SS, Ghofrani HA, Samidurai A, Traupe H, Seeger W, Grimminger F, Schermuly RT. Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury. BMC Pulm Med. 2008 Dec 17;8:25. doi: 10.1186/1471-2466-8-25. PMID:19087359 doi:http://dx.doi.org/10.1186/1471-2466-8-25
  3. ↑ Osiezagha K, Ali S, Freeman C, Barker NC, Jabeen S, Maitra S, Olagbemiro Y, Richie W, Bailey RK. Thiamine deficiency and delirium. Innov Clin Neurosci. 2013 Apr;10(4):26-32. PMID:23696956
  4. ↑ Kerns JC, Arundel C, Chawla LS. Thiamin deficiency in people with obesity. Adv Nutr. 2015 Mar 13;6(2):147-53. doi: 10.3945/an.114.007526. Print 2015 Mar. PMID:25770253 doi:http://dx.doi.org/10.3945/an.114.007526
  5. ↑ Barennes H, Sengkhamyong K, Rene JP, Phimmasane M. Beriberi (thiamine deficiency) and high infant mortality in northern Laos. PLoS Negl Trop Dis. 2015 Mar 17;9(3):e0003581. doi: 10.1371/journal.pntd.0003581., eCollection 2015 Mar. PMID:25781926 doi:http://dx.doi.org/10.1371/journal.pntd.0003581
  6. ↑ Homewood J, Bond NW. Thiamin deficiency and Korsakoff's syndrome: failure to find memory impairments following nonalcoholic Wernicke's encephalopathy. Alcohol. 1999 Aug;19(1):75-84. PMID:10487391
  7. ↑ Chiu HJ, Reddick JJ, Begley TP, Ealick SE. Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 A resolution. Biochemistry. 1999 May 18;38(20):6460-70. PMID:10350464 doi:http://dx.doi.org/10.1021/bi982903z

Thiamin phosphate synthase complex with reaction products thiamin phosphate, pyrophosphate and Mg+2 ion (green) (PDB code 2tps)

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=Thiamin_phosphate_synthase&oldid=4206168"