Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a covalent inhibitor N-[(3R,4R)-4-fluoro-1-{6-[(3-methoxy-1-methyl-1H-pyrazol-4-yl)amino]-9-(propan-2-yl)-9H-purin-2-yl}pyrrolidin-3-yl]propanamide. Determined by X-ray diffraction at 1.33 Å resolution. Released 22 Mar 2017.
Explore 5UG9 in 3D Show helices and sheets RCSB PDB PDBe
5UG9 contains 20 α-helices and 17 β-strands across 1 chain. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.
| Element | Residues | Length | Sheet |
|---|---|---|---|
| β-strand | 705-706 | 2 | 1 |
| α-helix | 709-711 | 3 | |
| β-strand | 712-721 | 10 | 1 |
| β-strand | 724-731 | 8 | 1 |
| β-strand | 740-747 | 8 | 1 |
| α-helix | 756-767 | 12 | |
| β-strand | 771 | 1 | 2 |
| β-strand | 774 | 1 | 2 |
| α-helix | 775-776 | 2 | |
| β-strand | 777-782 | 6 | 1 |
| β-strand | 786-791 | 6 | 1 |
| β-strand | 797 | 1 | 2 |
| α-helix | 798-804 | 7 | |
| α-helix | 806-808 | 3 | |
| α-helix | 811-830 | 20 | |
| β-strand | 833-834 | 2 | 3 |
| α-helix | 840-842 | 3 | |
| β-strand | 843-847 | 5 | 2 |
| β-strand | 850-853 | 4 | 2 |
| β-strand | 860-861 | 2 | 3 |
| α-helix | 862-863 | 2 | |
| β-strand | 869-870 | 2 | 4 |
| α-helix | 878-880 | 3 | |
| α-helix | 883-888 | 6 | |
| β-strand | 890-891 | 2 | 4 |
| α-helix | 893-908 | 16 | |
| α-helix | 912-913 | 2 | |
| α-helix | 920-922 | 3 | |
| α-helix | 923-928 | 6 | |
| α-helix | 933-936 | 4 | |
| β-strand | 939 | 1 | 5 |
| α-helix | 941-950 | 10 | |
| α-helix | 955-957 | 3 | |
| α-helix | 959-960 | 2 | |
| α-helix | 961-972 | 12 | |
| α-helix | 975-977 | 3 | |
| β-strand | 979 | 1 | 5 |
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|---|---|---|---|---|
| Epidermal growth factor receptor | A | protein | 329 | Homo sapiens | P00533 (AlphaFold model) |
>5UG9_1 Epidermal growth factor receptor (chains A) GSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSP KANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLIMQLMPFGCLLDYVREHKDNIGSQY LLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGRAKLLGAEEKEYHAEG GKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERL PQPPICTIDVYMIMRKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPT DSNFYRALMDEEDMDDVVDADEYLIPQQG
| ID | Name | Formula | Copies |
|---|---|---|---|
| 8AM | N-[(3R,4R)-4-fluoro-1-{6-[(3-methoxy-1-methyl-1H-pyrazol-4-yl)amino]-9-(propan-… | C20 H28 F N9 O2 | 1 |
Water and common crystallization additives (EDO, GOL, SO4) are not listed.
Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR. Planken, S., Behenna, D.C., Nair, S.K. et al. J Med Chem (2017) 60:3002-3019. DOI 10.1021/acs.jmedchem.6b01894 · PubMed
Other PDB entries of the same protein (UniProt P00533 (AlphaFold model), which also has an AlphaFold model), best resolution first:
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