Thiamin phosphate synthase

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== Function ==
== Function ==
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'''Thiamin phosphate synthase''' (TPS) 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<ref>PMID:11513588</ref>
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'''Thiamin phosphate synthase''' (TPS) 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<ref>PMID:11513588</ref>.
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== Disease ==
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== Relevance ==
== Relevance ==
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Thiamin is an essential component of human diet. Thiamin deficiency is associated with neurodegenerative diseases<ref>PMID:19087359</ref>, delirium<ref>PMID:23696956</ref>, obesity<ref>PMID:25770253</ref> and results in beriberi<ref>PMID:25781926</ref> and in the alcoholic brain disease Korsakoff's syndrome<ref>PMID:10487391</ref>. TPS is involved in thiamin biosynthesis.
== Structural highlights ==
== Structural highlights ==
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The active site pocket of TPS is formed by three loop regions. TPS reaction products thiamin phosphate and pyrophosphate interact with various residues of the protein as well as with each other<ref>PMID:10350464</ref>.
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</StructureSection>

Revision as of 08:24, 12 November 2018

Caption for this structure

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3D structures of thiamin phosphate synthase

Updated on 12-November-2018

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

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

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Alexander Berchansky, Michal Harel

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