Substrate-to-Product Conversion Facilitates Active Site Loop Opening in Yeast Enolase: A Molecular Dynamics Study

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Abstract

Yeast enolase serves as a prototype for metalloenzymes with labile, catalytically active site metal ions and is important for glycolysis and fermentation processes. Herein, microsecond molecular dynamics simulations of the protein-substrate and protein-product complexes are conducted to elucidate the mechanism of the opening of catalytically important active site loops. These simulations indicate that conversion of substrate to product is accompanied by diminished metal coordination and hydrogen-bonding interactions, as well as enhanced loop flexibility. Moreover, free-energy simulations show that the loop opening is endergonic when substrate is bound but exergonic when product is bound. Thus, the conversion to product weakens the association of the loop with the ligand and binding site, thereby facilitating the loop opening after catalysis and enabling product release. These insights about active site loop motions in enzyme catalysis may be useful in guiding enzyme design efforts.

Original languageEnglish (US)
Pages (from-to)8985-8990
Number of pages6
JournalACS Catalysis
Volume9
Issue number10
DOIs
StatePublished - Oct 4 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry

Keywords

  • catalysis
  • enolase
  • hydrogen bond
  • loop motions
  • metalloenzymes

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