A new crystal form of mouse thiamin pyrophosphokinase

Jing Yuan Liu, Thomas Hurley

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Thiamin pyrophosphokinase (TPK) transfers a pyrophosphate group from ATP to the hydroxyl group of thiamin and produces thiamin pyrophosphate (TPP). TPP is the cofactor of metabolically important enzymes such as pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, transketolase and 2-hydroxyphytanoyl-CoA lyase. Thiamin deficiency results in Wernike-Korsakof Syndrome (WKS) due to neurological disorder and wet beriberi, a potentially fatal cardiovascular disease. Mouse TPK associates as a dimer revealed by previous solved crystallographic structures. In this study, we report mouse TPK complexed with TPP-Mg2+ and thiamin -Mg2+, respectively, in a new crystal form. In these two structures, four mouse TPK molecules were found in each asymmetric unit. Although we cannot rule out this tetramer form can be an artifact from crystal packing, mouse TPK tetramer has a more closed ATP binding pocket and has the potential to provide specific interactions between mouse TPK and ATP compared with the previous dimeric structure and is likely to be an active form.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalInternational Journal of Biochemistry and Molecular Biology
Volume2
Issue number2
StatePublished - 2011

Fingerprint

Thiamin Pyrophosphokinase
Thiamine Pyrophosphate
Crystals
Thiamine
Adenosine Triphosphate
Oxidoreductases
Beriberi
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Transketolase
Thiamine Deficiency
Nervous System Diseases
Pyruvic Acid
Hydroxyl Radical
Dimers
Artifacts
Cardiovascular Diseases
Molecules

Keywords

  • Crystal structure
  • Dimer
  • Protein oligomerization
  • Tetramer
  • Thiamin pyrophosphokinase (TPK)
  • Thiamin-Mg
  • TPP-Mg

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

A new crystal form of mouse thiamin pyrophosphokinase. / Liu, Jing Yuan; Hurley, Thomas.

In: International Journal of Biochemistry and Molecular Biology, Vol. 2, No. 2, 2011, p. 111-118.

Research output: Contribution to journalArticle

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