5O8V
Covalent Inhibitor 4a bound to the Lipid Pocket of p38alpha Mutant S251C
Summary for 5O8V
| Entry DOI | 10.2210/pdb5o8v/pdb |
| Descriptor | Mitogen-activated protein kinase 14, ~{N}-[3-[7-azanyl-4-(2-phenylethylamino)quinazolin-2-yl]phenyl]propanamide (3 entities in total) |
| Functional Keywords | kinase, small molecule, lipid pocket, p38, covalent, mutant, transferase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm : Q16539 |
| Total number of polymer chains | 1 |
| Total formula weight | 41770.76 |
| Authors | Buehrmann, M.,Rauh, D. (deposition date: 2017-06-14, release date: 2017-09-06, Last modification date: 2024-10-23) |
| Primary citation | Buhrmann, M.,Hardick, J.,Weisner, J.,Quambusch, L.,Rauh, D. Covalent Lipid Pocket Ligands Targeting p38 alpha MAPK Mutants. Angew. Chem. Int. Ed. Engl., 56:13232-13236, 2017 Cited by PubMed Abstract: A chemical genetic approach is presented to covalently target a unique lipid binding pocket in the protein kinase p38α, whose function is not yet known. Based on a series of cocrystal structures, a library of 2-arylquinazolines that were decorated with electrophiles were designed and synthesized to covalently target tailored p38α mutants containing artificially introduced cysteine residues. Matching protein-ligand pairs were identified by MS analysis and further validated by MS/MS studies and protein crystallography. The covalent ligands that emerged from this approach showed excellent selectivity towards a single p38α mutant and will be applicable as suitable probes in future studies of biological systems to dissect the function of the lipid pocket by means of pharmacological perturbations. PubMed: 28834017DOI: 10.1002/anie.201706345 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
Download full validation report
