9DF4 | pdb_00009df4

EGFR Exon20 insertion mutant SVD bound with STX-721

PDB DOI: https://doi.org/10.2210/pdb9DF4/pdb

Classification: ONCOPROTEIN,TRANSFERASE/TRANSFERASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): Yes

Deposited: 2024-08-29 Released: 2025-05-14
Deposition Author(s): Hilbert, B.J., Brooijmans, N., Pagliarini, R.A., Milgram, B.C.
Funding Organization(s): Not funded

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.78 ?
R-Value Free:
0.198 (Depositor), 0.209 (DCC)
R-Value Work:
0.166 (Depositor), 0.178 (DCC)
R-Value Observed:
0.167 (Depositor)

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

This is version 1.0 of the entry. See complete history.

Literature

STX-721, a covalent EGFR/HER2 exon 20 inhibitor, takes advantage of exon 20 mutant dynamic protein states and achieves unique mutant-selectivity across human cancer models

Pagliarini, R.A., Henderson, J.A., Borrelli, D.R., Brooijmans, N., Hilbert, B.J., Huff, M.R., Ito, T., Kryukov, G., Ladd, B., Martin, B., Milgram, B.C., Motiwala, H., OHearn, E., Wang, W., Hata, A., Bellier, J., Kuzmic, P., Guzman-Perez, A., Jackson, E.L., Stuart, D.

To be published.

Macromolecule Content

Total Structure Weight: 40.07 kDa
Atom Count: 2,863
Modelled Residue Count: 308
Deposited Residue Count: 333
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Epidermal growth factor receptor	A	333	Homo sapiens	Mutation(s): 1 Gene Names: EGFR, ERBB, ERBB1, HER1 EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00533 (Homo sapiens) Explore P00533 Go to UniProtKB: P00533
PHAROS: P00533 GTEx: ENSG00000146648
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00533
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
A1A4E (Subject of Investigation/LOI) Query on A1A4E Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	(2P)-3-(3-chloro-2-methoxyanilino)-2-[3-({(2R)-1-[(2E)-4-(dimethylamino)but-2-enoyl]-2-methylpyrrolidin-2-yl}ethynyl)pyridin-4-yl]-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one C₃₂ H₃₅ Cl N₆ O₃ UMSJPISUMQOUKS-LMZGTLAXSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain P [auth A] SDF format, chain Q [auth A] SDF format, chain S [auth A] SDF format, chain T [auth A] SDF format, chain U [auth A] SDF format, chain V [auth A] SDF format, chain Y [auth A] SDF format, chain R [auth A] SDF format, chain W [auth A] SDF format, chain X [auth A] MOL2 format, chain P [auth A] MOL2 format, chain Q [auth A] MOL2 format, chain S [auth A] MOL2 format, chain T [auth A] MOL2 format, chain U [auth A] MOL2 format, chain V [auth A] MOL2 format, chain Y [auth A] MOL2 format, chain R [auth A] MOL2 format, chain W [auth A] MOL2 format, chain X [auth A] mmCIF format, chain P [auth A] mmCIF format, chain Q [auth A] mmCIF format, chain S [auth A] mmCIF format, chain T [auth A] mmCIF format, chain U [auth A] mmCIF format, chain V [auth A] mmCIF format, chain Y [auth A] mmCIF format, chain R [auth A] mmCIF format, chain W [auth A] mmCIF format, chain X [auth A]	P [auth A] Q [auth A] R [auth A] S [auth A] T [auth A] P [auth A], Q [auth A], R [auth A], S [auth A], T [auth A], U [auth A], V [auth A], W [auth A], X [auth A], Y [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A] Interactions & Density Focus chain P [auth A] Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Focus chain V [auth A] Focus chain W [auth A] Focus chain X [auth A] Focus chain Y [auth A]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain K [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain J [auth A] SDF format, chain L [auth A] SDF format, chain O [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain K [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain J [auth A] MOL2 format, chain L [auth A] MOL2 format, chain O [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain K [auth A] mmCIF format, chain M [auth A] mmCIF format, chain N [auth A] mmCIF format, chain J [auth A] mmCIF format, chain L [auth A] mmCIF format, chain O [auth A]	G [auth A] H [auth A] I [auth A] J [auth A] K [auth A] G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A], N [auth A], O [auth A]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain C [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] MOL2 format, chain D [auth A] MOL2 format, chain C [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] mmCIF format, chain D [auth A] mmCIF format, chain C [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A]	C [auth A], D [auth A], E [auth A], F [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A]