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].
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- . Water molecules are shown as red spheres.
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3D structures of thiamin phosphate synthase
Updated on 18-August-2024
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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
