Divergent evolution of enzymatic function: Mechanistically diverse superfamilies and functionally distinct suprafamilies

J. A. Gerlt, P. C. Babbitt

Research output: Contribution to journalReview article

Abstract

The protein sequence and structure databases are now sufficiently representative that strategies nature uses to evolve new catalytic functions can be identified. Groups of divergently related enzymes whose members catalyze different reactions but share a common partial reaction, intermediate, or transition state (mechanistically diverse superfamilies) have been discovered, including the enolase, amidohydrolase, thiyl radical, crotonase, vicinal-oxygen-chelate, and Fe-dependent oxidase superfamilies. Other groups of divergently related enzymes whose members catalyze different overall reactions that do not share a common mechanistic strategy (functionally distinct suprafamilies) have also been identified: (a) functionally distinct suprafamilies whose members catalyze successive transformations in the tryptophan and histidine biosynthetic pathways and (b) functionally distinct suprafamilies whose members catalyze different reactions in different metabolic pathways. An understanding of the structural bases for the catalytic diversity observed in super- and suprafamilies may provide the basis for discovering the functions of proteins and enzymes in new genomes as well as provide guidance for in vitro evolution/engineering of new enzymes.

Original languageEnglish (US)
Pages (from-to)209-246
Number of pages38
JournalAnnual review of biochemistry
Volume70
DOIs
StatePublished - Jul 30 2001

Keywords

  • (β/α)-barrels
  • Amidohydrolase
  • Crotonase
  • Enolase
  • Thiyl radical

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Divergent evolution of enzymatic function: Mechanistically diverse superfamilies and functionally distinct suprafamilies'. Together they form a unique fingerprint.

  • Cite this