Methods for discovering catalytic activities for pseudokinases

Miles H. Black, Marcin Gradowski, Krzysztof Pawłowski, Vincent S. Tagliabracci

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Pseudoenzymes resemble active enzymes, but lack key catalytic residues believed to be required for activity. Many pseudoenzymes appear to be inactive in conventional enzyme assays. However, an alternative explanation for their apparent lack of activity is that pseudoenzymes are being assayed for the wrong reaction. We have discovered several new protein kinase-like families which have revealed how different binding orientations of adenosine triphosphate (ATP) and active site residue migration can generate a novel reaction from a common kinase scaffold. These results have exposed the catalytic versatility of the protein kinase fold and suggest that atypical kinases and pseudokinases should be analyzed for alternative transferase activities. In this chapter, we discuss a general approach for bioinformatically identifying divergent or atypical members of an enzyme superfamily, then present an experimental approach to characterize their catalytic activity.

Original languageEnglish (US)
Title of host publicationPseudokinases
EditorsNatalia Jura, James M. Murphy
PublisherAcademic Press Inc.
Pages575-610
Number of pages36
ISBN (Print)9780323915410
DOIs
StatePublished - Jan 2022

Publication series

NameMethods in Enzymology
Volume667
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • Atypical kinases
  • Bioinformatics
  • Pseudokinases
  • Uncharacterized proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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