A thiamin diphosphate binding fold revealed by comparison of the crystal structures of transketolase, pyruvate oxidase and pyruvate decarboxylase

Yves A. Muller, Ylva Lindqvist, William Furey, Georg E. Schulz, Frank Jordan, Gunter Schneider

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

Background: The crystal structures of three thiamin diphosphate-dependent enzymes that catalyze distinct reactions in basic metabolic pathways are known. These enzymes - transketolase, pyruvate oxidase and pyruvate decarboxylase - also require metal ions such as Ca2+ and Mg2+ as cofactors and have little overall sequence similarity. Here, the crystal structures of these three enzymes are compared. Results: The three enzymes share a similar pattern of binding of thiamin diphosphate and the metal ion cofactors. The enzymes function as multisubunit proteins, with each polypeptide chain folded into three α β domains. Two of these domains are involved in binding of the thiamin diphosphate and the metal ion. These domains have the same topology of six parallel β-strands and surrounding α-helices. The thiamin diphosphate is bound in a cleft, formed by two domains from two different subunits. Only a few residues are conserved in all three enzymes and these are responsible for proper binding of the cofactors. Conclusions: Despite considerable differences in quaternary structure and lack of overall sequence homology, thiamin diphosphate binds to the three enzymes in a very similar fashion, and a general thiamin-binding fold can be revealed.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalStructure
Volume1
Issue number2
DOIs
StatePublished - Oct 15 1993

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

  • pyruvate decarboxylase
  • pyruvate oxidase
  • structure comparison
  • thiamin diphosphate
  • transketolase

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