Enhanced Preprints

Allosteric regulation of kinase activity in living cells

  1. Shivani Godbole
  2. Nikolay V. Dokholyan author has email address
  1. Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033-0850, USA
  2. Department of Biomedical Engineering, Penn State University, University Park, PA 16802, USA
  3. Department of Engineering Science and Mechanics, Penn State University, University Park, PA 16802, USA
  4. Department of Biochemistry & Molecular Biology, Penn State College of Medicine, Hershey, PA 17033-0850, USA
  5. Department of Chemistry, Penn State University, University Park, PA 16802, USA

Peer review process

Revised: This Reviewed Preprint has been revised by the authors in response to the previous round of peer review; the eLife assessment and the public reviews have been updated where necessary by the editors and peer reviewers.

Read more about eLife’s peer review process.

Editors

  • Reviewing Editor
    Volker Dötsch
    Goethe University Frankfurt, Frankfurt am Main, Germany
  • Senior Editor
    Volker Dötsch
    Goethe University Frankfurt, Frankfurt am Main, Germany

Joint Public Review:

This concise review provides a clear and instructive picture of the state-of-the-art understanding of protein kinases' activity and sets of approaches and tools to analyse and regulate it.

Three major parts of the work include: methods to map allosteric communications, tools to control allostery, and allosteric regulation of protein kinases. The work provides an important and timely view of the current status of our understanding of the function of protein kinases and state-of-the-art methods to study its allosteric regulation and to develop allosteric approaches to control it.

Author Response

The following is the authors’ response to the previous reviews

Comments from reviewer 1:

Comment 1. Regarding SBSMMA, the authors may complement their discussion by mentioning recent work (PMID: 35738428) where SBSMMA was used to exemplify a potential fragment-based design approach for developing allosteric effectors for kinases.

Thank you for the suggestion, we have added a short summary of the work where SBSMMA is used as a basis for developing small molecules to target kinases using fragment-based design approach

  1. Howard Hughes Medical Institute
  2. Wellcome Trust
  3. Max-Planck-Gesellschaft
  4. Knut and Alice Wallenberg Foundation