Arabinose 5-phosphate covalently inhibits transaldolase

Samuel H. Light, Wayne F. Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Arabinose 5-phosphate (A5P) is the aldopentose version of the ketohexose fructose 6-phosphate (F6P), having identical stereochemistry but lacking atoms corresponding to the 1-carbon and 1-hydroxyl. Despite structural similarity and conservation of the reactive portion of F6P, F6P acts as a substrate whereas A5P is reported to be an inhibitor of transaldolase. To address the lack of A5P reactivity we determined a crystal structure of the Francisella tularensis transaldolase in complex with A5P. This structure reveals that like F6P, A5P forms a covalent Schiff base with active site Lys135. Unlike F6P, A5P binding fails to displace an ordered active site water molecule. Retaining this water necessitates conformational changes at the A5P-protein linkage that possibly hinder reactivity. The findings presented here show the basis of A5P inhibition and suggest an unusual mechanism of competitive, reversible-covalent transaldolase regulation.

Original languageEnglish (US)
Pages (from-to)41-44
Number of pages4
JournalJournal of Structural and Functional Genomics
Volume15
Issue number1
DOIs
StatePublished - Mar 2014

Keywords

  • Arabinose 5-phosphate
  • Competitive inhibition
  • Glucose 6-phosphate
  • Ordered water
  • Pentose phosphate pathway
  • X-ray crystal structure

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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