Cooperativity and flexibility in enzyme evolution

Curr Opin Struct Biol. 2018 Feb:48:83-92. doi: 10.1016/j.sbi.2017.10.020. Epub 2017 Nov 12.

Abstract

Enzymes are flexible catalysts, and there has been substantial discussion about the extent to which this flexibility contributes to their catalytic efficiency. What has been significantly less discussed is the extent to which this flexibility contributes to their evolvability. Despite this, recent years have seen an increasing number of both experimental and computational studies that demonstrate that cooperativity and flexibility play significant roles in enzyme innovation. This review covers key developments in the field that emphasize the importance of enzyme dynamics not just to the evolution of new enzyme function(s), but also as a property that can be harnessed in the design of new artificial enzymes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Aryldialkylphosphatase / chemistry*
  • Aryldialkylphosphatase / metabolism
  • Bacteria / classification
  • Bacteria / enzymology
  • Biocatalysis
  • Catalytic Domain
  • Evolution, Molecular*
  • Humans
  • Models, Molecular
  • Phosphoric Monoester Hydrolases / chemistry*
  • Phosphoric Monoester Hydrolases / metabolism
  • Phylogeny
  • Protein Conformation
  • Structure-Activity Relationship
  • Substrate Specificity
  • Tetrahydrofolate Dehydrogenase / chemistry*
  • Tetrahydrofolate Dehydrogenase / metabolism
  • beta-Lactamases / chemistry*
  • beta-Lactamases / metabolism

Substances

  • Tetrahydrofolate Dehydrogenase
  • Phosphoric Monoester Hydrolases
  • Aryldialkylphosphatase
  • PON1 protein, human
  • beta-Lactamases