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Abstract Functional regulation of cell signaling through dynamic changes in protein activity state as well as spatial organization represent two dynamic, complex, and conserved phenomena in biology. Seemingly separate areas of ‐omics method development have focused on building tools that can detect and quantify protein activity states, as well as map sub‐cellular and intercellular protein organization. Integration of these efforts, through the development of chemical tools and platforms that enable detection and quantification of protein functional states with spatial resolution provide opportunities to better understand heterogeneity in the proteome within cell organelles, multi‐cellular tissues, and whole organisms. This review provides an overview of and considerations for major classes of chemical proteomic probes and technologies that enable protein activity mapping from sub‐cellular compartments to live animals.
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Advances in Activity‐Based Protein Profiling of Functional Tyrosines in Proteomes
Abstract Activity‐based protein profiling (ABPP) is a chemical proteomic method for investigating functional states of proteins in native biological settings. By quantifying changes in probe binding states of active and regulatory protein sites, ABPP reveals functional information on protein regulation and can be configured in competitive settings to determine global selectivity profiles of tool compounds and drugs in lysates, cells, and animals. Chemical probes used for ABPP analyses can target protein families with conserved enzymatic or structural features or can broadly profile the proteome using electrophiles with reactivity towards functional groups on amino acid side chains. The latter approach has provided insights to protein sites involved in allosteric regulation and non‐enzymatic functions. This review introduces quantitative ABPP workflows and discusses electrophilic groups used for ABPP profiling of functional sites in the proteome with an emphasis on tyrosine residues.
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- PAR ID:
- 10506259
- Publisher / Repository:
- Wiley‐VCH
- Date Published:
- Journal Name:
- Israel Journal of Chemistry
- Volume:
- 63
- Issue:
- 3-4
- ISSN:
- 0021-2148
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/ijch.202300001
