Chemical Proteomic Profiling of Protein 4′‐Phosphopantetheinylation in Mammalian Cells
Protein 4′‐phosphopantetheinylation is an essential post‐translational modification (PTM) in prokaryotes and eukaryotes. So far, only five protein substrates of this specific PTM have been discovered in mammalian cells. These proteins are known to perform important functions, including fatty acid bi...
Saved in:
Published in | Angewandte Chemie International Edition Vol. 59; no. 37; pp. 16069 - 16075 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
WEINHEIM
Wiley
07.09.2020
Wiley Subscription Services, Inc |
Edition | International ed. in English |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Protein 4′‐phosphopantetheinylation is an essential post‐translational modification (PTM) in prokaryotes and eukaryotes. So far, only five protein substrates of this specific PTM have been discovered in mammalian cells. These proteins are known to perform important functions, including fatty acid biosynthesis and folate metabolism, as well as β‐alanine activation. To explore existing and new substrates of 4′‐phosphopantetheinylation in mammalian proteomes, we designed and synthesized a series of new pantetheine analogue probes, enabling effective metabolic labelling of 4′‐phosphopantetheinylated proteins in HepG2 cells. In combination with a quantitative chemical proteomic platform, we enriched and identified all the currently known 4′‐phosphopantetheinylated proteins with high confidence, and unambiguously determined their exact sites of modification. More encouragingly, we discovered, using targeted chemical proteomics, a potential 4′‐phosphopantetheinylation site in the protein of mitochondrial dehydrogenase/reductase SDR family member 2 (DHRS2).
By developing a new generation of pantetheine analogue probes, the metabolic labelling and chemoproteomic profiling of protein 4′‐phosphopantetheinylation in mammalian cells were achieved. Targeted chemical proteomics facilitated the identification of exact 4′‐phosphopantetheinylation sites, including all five currently known sites and a potential site in the mitochondrial dehydrogenase/reductase SDR family member 2 (DHRS2). |
---|---|
Bibliography: | Dedicated to Professor Youqi Tang on the occasion of his 100th birthday ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1433-7851 1521-3773 |
DOI: | 10.1002/anie.202004105 |