Catalytic Roles of Histidine and Arginine in Pyruvate Class II Aldolase: A Perspective from QM/MM Metadynamics

Gou Tao Huang, Jen-Shiang Yu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The retro-aldol reaction catalyzed by pyruvate class II aldolase is investigated with QM/MM metadynamics; this enzyme transforms the substrate of 4-hydroxy-2-ketoacid into pyruvate and aldehyde through the aldol cleavage. The hydroxyl group of the substrate is deprotonated by His45 with the aid of the metal-bound water, while the metal-bound hydroxide proposed in the literature is observed as a transient species. The deprotonation appears to enhance substrate binding between the deprotonated substrate and the active site. The reactive alkoxide is further stabilized by the salt bridge of Arg70-Asp42, facilitating the following aldol cleavage. The simulations show that the C-C bond cleavage is the rate-determining step, and the calculated barrier of approximately 14 kcal mol-1 agrees reasonably with experimental data.

Original languageEnglish
Pages (from-to)8130-8133
Number of pages4
JournalACS Catalysis
Volume7
Issue number12
DOIs
StatePublished - 1 Dec 2017

Keywords

  • aldol cleavage
  • aldolase
  • metadynamics
  • pyruvate
  • QM/MM
  • salt bridge

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