Article ; Online: A novel yeast-based high-throughput method for the identification of protein palmitoylation inhibitors.
2021 Volume 11, Issue 8, Page(s) 200415
Abstract: Protein S-acylation or palmitoylation is a widespread post-translational modification that consists of the addition of a lipid molecule to cysteine residues of proteins through a thioester bond. Palmitoylation and palmitoyltransferases (PATs) have been ... ...
| Abstract | Protein S-acylation or palmitoylation is a widespread post-translational modification that consists of the addition of a lipid molecule to cysteine residues of proteins through a thioester bond. Palmitoylation and palmitoyltransferases (PATs) have been linked to several types of cancers, diseases of the central nervous system and many infectious diseases where pathogens use the host cell machinery to palmitoylate their effectors. Despite the central importance of palmitoylation in cell physiology and disease, progress in the field has been hampered by the lack of potent-specific inhibitors of palmitoylation in general, and of individual PATs in particular. Herein, we present a yeast-based method for the high-throughput identification of small molecules that inhibit protein palmitoylation. The system is based on a reporter gene that responds to the acylation status of a palmitoylation substrate fused to a transcription factor. The method can be applied to heterologous PATs such as human DHHC20, mouse DHHC21 and also a PAT from the parasite |
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| MeSH term(s) | Acyltransferases/antagonists & inhibitors ; Animals ; Giardia lamblia/drug effects ; Giardia lamblia/growth & development ; Giardia lamblia/metabolism ; High-Throughput Screening Assays ; Humans ; Lipoylation ; Mice ; Protozoan Proteins/antagonists & inhibitors ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/growth & development ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/antagonists & inhibitors ; Small Molecule Libraries/pharmacology ; Substrate Specificity |
| Chemical Substances | Protozoan Proteins ; Saccharomyces cerevisiae Proteins ; Small Molecule Libraries ; Acyltransferases (EC 2.3.-) ; ZDHHC20 protein, human (EC 2.3.-) ; AKR1 protein, S cerevisiae (EC 2.3.1.-) |
| Language | English |
| Publishing date | 2021-08-04 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2630944-0 |
| ISSN | 2046-2441 ; 2046-2441 |
| ISSN (online) | 2046-2441 |
| ISSN | 2046-2441 |
| DOI | 10.1098/rsob.200415 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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