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Methods for discovering catalytic activities for pseudokinases.

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.

SUBMITTER: Black MH

PROVIDER: S-EPMC9554938 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Methods for discovering catalytic activities for pseudokinases.

Black Miles H MH Gradowski Marcin M Pawłowski Krzysztof K Tagliabracci Vincent S VS

Methods in enzymology 20220418

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 ca ...[more]

PMID: 35525554

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Project description:This SuperSeries is composed of the SubSeries listed below.

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