Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5
Scripps Research Institute · Scripps Clinic · +6 more institutions
Abstract
Adaptors serve as hubs to regulate diverse protein complexes in cells. This multitude of functions can complicate the study of adaptors, as their genetic disruption may simultaneously impair the activities of several compositionally distinct complexes (or adaptor 'complexoforms'). Here we describe the chemical proteomic discovery of bicyclopyrrolidine acrylamide stereoprobes that react with C100 of the methyltransferase (MT) adaptor TRMT112 in human cells. Curiously, the stereoprobes showed negligible reactivity with uncomplexed recombinant TRMT112 and we found that this interaction was restored exclusively in the presence of METTL5 but not other MTs. A cocrystal structure revealed stereoprobe binding to a…
Citation impact
- FWCI
- 37.62
- Percentile
- 99%
- References
- 76
Authors
10- FWF. Wieland GoetzkeCorresponding
Scripps Research Institute, Scripps Clinic
- SMSteffen M. Bernard
Vividion Therapeutics (United States)
- CJCheng-Wei Ju
University of Chicago
- JPJonathan Pollock
Vividion Therapeutics (United States)
- KEKristen E. DeMeester
Scripps Institution of Oceanography, Scripps (United States)
Topics & keywords
- Allosteric regulation
- Signal transducing adaptor protein
- Cocrystal
- Covalent bond
- Reactivity (psychology)
- Chemical biology
- Plasma protein binding
- Protein–protein interaction