8A2D: EGFR kinase domain

EGFR kinase domain (L858R/V948R) in complex with 2-[4-(difluoromethyl)-6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl]methyl]phenyl]ethynyl]-7-methyl-indazol-2-yl]-2-spiro[6,7-dihydropyrrolo[1,2-c]imidazole-5,1'-cyclopropane]-1-yl-N-thiazol-2-yl-acetamide. Determined by X-ray diffraction at 1.11 Å resolution. Released 19 Oct 2022.

Method: X-ray diffraction
Resolution: 1.11 Å
Organism: Homo sapiens
Chains: 1
Atoms: 2,770
Mol. weight: 38.27 kDa
Ligands: KXY
Released: 19 Oct 2022

Explore 8A2D in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8A2D contains 21 α-helices and 13 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.

Chain A: 21 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	705-706	2	1
α-helix	709-711	3
β-strand	712-720	9	1
β-strand	724-731	8	1
β-strand	740-747	8	1
α-helix	753-767	15
β-strand	771	1	2
β-strand	774	1	2
α-helix	775-776	2
β-strand	777-781	5	1
β-strand	787-791	5	1
β-strand	797	1	2
α-helix	798-804	7
α-helix	806-808	3
α-helix	811-830	20
α-helix	840-842	3
β-strand	843-847	5	2
β-strand	850-853	4	2
α-helix	866-868	3
α-helix	878-880	3
α-helix	883-888	6
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	3
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	3
α-helix	1018-1020	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Epidermal growth factor receptor	A	protein	326	Homo sapiens	P00533 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8A2D_1 Epidermal growth factor receptor (chains A)
GSMNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKAN
KEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLN
WCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGRAKLLGAEEKEYHAEGGKV
PIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQP
PICTIDVYMIMRKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSN
FYRALMDEEDMDDVVDADEYLIPQQG

Ligands and cofactors

ID	Name	Formula	Copies
KXY	(2R)-2-[4-[bis(fluoranyl)methyl]-6-[2-[4-[[4-(hydroxymethyl)piperidin-1-yl]meth…	C37 H37 F2 N7 O2 S	1

Water and common crystallization additives (EDO, MES) are not listed.

Primary citation

Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib. Obst-Sander, U., Ricci, A., Kuhn, B. et al. J Med Chem (2022) 65:13052-13073. DOI 10.1021/acs.jmedchem.2c00893 · PubMed

Other PDB entries of the same protein (UniProt P00533 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8A27 1.07 Å, EGFR kinase domain in complex with 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-[6-[2…
5UG9 1.33 Å, Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a…
5HG8 1.42 Å, EGFR (L858R, T790M, V948R) in complex with N-[3-({2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-…
8A2A 1.43 Å, EGFR kinase domain in complex with 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-[6-[2…
5UG8 1.46 Å, Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a…
3POZ 1.5 Å, EGFR Kinase domain complexed with tak-285
6TFV 1.5 Å, Crystal Structure of EGFR T790M/V948R in Complex with Covalent Pyrrolopyrimidine 18b
6TG0 1.5 Å, Crystal Structure of EGFR T790M/V948R in Complex with Covalent Pyrrolopyrimidine 21a
3VRP 1.52 Å, Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with…
5HG5 1.52 Å, EGFR (L858R, T790M, V948R) in complex with N-{3-[(2-{[4-(4-methylpiperazin-1-yl)phenyl]am…
5CNO 1.55 Å, Crystal structure of the EGFR kinase domain mutant V924R
9NTP 1.55 Å, EGFR kinase domain (T790MV948R) in complex with a strain-release covalent inhibitor

Browse structure collections

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