Computational, structural, and kinetic evidence that Vibrio vulnificus FrsA is not a cofactor-independent pyruvate decarboxylase

Whitney F. Kellett, Elizabeth Brunk, Bijoy J. Desai, Alexander A. Fedorov, Steven C. Almo, John A. Gerlt, Ursula Rothlisberger, Nigel G.J. Richards

Research output: Contribution to journalArticle

Abstract

The fermentation-respiration switch (FrsA) protein in Vibrio vulnificus was recently reported to catalyze the cofactor-independent decarboxylation of pyruvate. We now report quantum mechanical/molecular mechenical calculations that examine the energetics of C-C bond cleavage for a pyruvate molecule bound within the putative active site of FrsA. These calculations suggest that the barrier to C-C bond cleavage in the bound substrate is 28 kcal/mol, which is similar to that estimated for the uncatalyzed decarboxylation of pyruvate in water at 25 °C. In agreement with the theoretical predictions, no pyruvate decarboxylase activity was detected for recombinant FrsA protein that could be crystallized and structurally characterized. These results suggest that the functional annotation of FrsA as a cofactor-independent pyruvate decarboxylase is incorrect.

Original languageEnglish (US)
Pages (from-to)1842-1844
Number of pages3
JournalBiochemistry
Volume52
Issue number11
DOIs
StatePublished - Mar 19 2013

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Kellett, W. F., Brunk, E., Desai, B. J., Fedorov, A. A., Almo, S. C., Gerlt, J. A., Rothlisberger, U., & Richards, N. G. J. (2013). Computational, structural, and kinetic evidence that Vibrio vulnificus FrsA is not a cofactor-independent pyruvate decarboxylase. Biochemistry, 52(11), 1842-1844. https://doi.org/10.1021/bi400093y