7JXP

EGFR kinase (T790M/V948R) in complex with osimertinib and JBJ-04-125-02

PDB DOI: https://doi.org/10.2210/pdb7JXP/pdb

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

Deposited: 2020-08-27 Released: 2021-09-08
Deposition Author(s): Beyett, T.S., Eck, M.J.
Funding Organization(s): National Institutes of Health/National Cancer Institute (NIH/NCI)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.16 Å
R-Value Free: 0.247
R-Value Work: 0.212
R-Value Observed: 0.214

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors

Beyett, T.S., To, C., Heppner, D.E., Rana, J.K., Schmoker, A.M., Jang, J., De Clercq, D.J.H., Gomez, G., Scott, D.A., Gray, N.S., Janne, P.A., Eck, M.J.

(2022) Nat Commun 13: 2530

DOI: https://doi.org/10.1038/s41467-022-30258-y

Macromolecule Content

Total Structure Weight: 232.73 kDa
Atom Count: 15,137
Modelled Residue Count: 1,783
Deposited Residue Count: 1,986
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 [auth D] B [auth A] C D [auth F] E [auth B] A [auth D], B [auth A], C, D [auth F], E [auth B], F [auth E]	331	Homo sapiens	Mutation(s): 2 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
JBJ (Subject of Investigation/LOI) Query on JBJ Download Ideal Coordinates CCD File SDF format, chain I [auth D] SDF format, chain L [auth A] SDF format, chain M [auth C] SDF format, chain Q [auth F] SDF format, chain T [auth B] SDF format, chain U [auth E] MOL2 format, chain I [auth D] MOL2 format, chain L [auth A] MOL2 format, chain M [auth C] MOL2 format, chain Q [auth F] MOL2 format, chain T [auth B] MOL2 format, chain U [auth E] mmCIF format, chain I [auth D] mmCIF format, chain L [auth A] mmCIF format, chain M [auth C] mmCIF format, chain Q [auth F] mmCIF format, chain T [auth B] mmCIF format, chain U [auth E]	I [auth D] L [auth A] M [auth C] Q [auth F] T [auth B] I [auth D], L [auth A], M [auth C], Q [auth F], T [auth B], U [auth E]	(2R)-2-(5-fluoro-2-hydroxyphenyl)-2-{1-oxo-6-[4-(piperazin-1-yl)phenyl]-1,3-dihydro-2H-isoindol-2-yl}-N-(1,3-thiazol-2-yl)acetamide C₂₉ H₂₆ F N₅ O₃ S VHQVOTINPRYDAO-AREMUKBSSA-N		Interactions Focus chain I [auth D] Focus chain L [auth A] Focus chain M [auth C] Focus chain Q [auth F] Focus chain T [auth B] Focus chain U [auth E] Interactions & Density Focus chain I [auth D] Focus chain L [auth A] Focus chain M [auth C] Focus chain Q [auth F] Focus chain T [auth B] Focus chain U [auth E]
ANP Query on ANP Download Ideal Coordinates CCD File SDF format, chain G [auth D] SDF format, chain J [auth A] SDF format, chain O [auth F] SDF format, chain R [auth B] MOL2 format, chain G [auth D] MOL2 format, chain J [auth A] MOL2 format, chain O [auth F] MOL2 format, chain R [auth B] mmCIF format, chain G [auth D] mmCIF format, chain J [auth A] mmCIF format, chain O [auth F] mmCIF format, chain R [auth B]	G [auth D], J [auth A], O [auth F], R [auth B]	PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER C₁₀ H₁₇ N₆ O₁₂ P₃ PVKSNHVPLWYQGJ-KQYNXXCUSA-N		Interactions Focus chain G [auth D] Focus chain J [auth A] Focus chain O [auth F] Focus chain R [auth B] Interactions & Density Focus chain G [auth D] Focus chain J [auth A] Focus chain O [auth F] Focus chain R [auth B]
YY3 (Subject of Investigation/LOI) Query on YY3 Download Ideal Coordinates CCD File SDF format, chain N [auth C] SDF format, chain V [auth E] MOL2 format, chain N [auth C] MOL2 format, chain V [auth E] mmCIF format, chain N [auth C] mmCIF format, chain V [auth E]	N [auth C], V [auth E]	N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide C₂₈ H₃₃ N₇ O₂ DUYJMQONPNNFPI-UHFFFAOYSA-N		Interactions Focus chain N [auth C] Focus chain V [auth E] Interactions & Density Focus chain N [auth C] Focus chain V [auth E]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain H [auth D] SDF format, chain K [auth A] SDF format, chain P [auth F] SDF format, chain S [auth B] MOL2 format, chain H [auth D] MOL2 format, chain K [auth A] MOL2 format, chain P [auth F] MOL2 format, chain S [auth B] mmCIF format, chain H [auth D] mmCIF format, chain K [auth A] mmCIF format, chain P [auth F] mmCIF format, chain S [auth B]	H [auth D], K [auth A], P [auth F], S [auth B]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain H [auth D] Focus chain K [auth A] Focus chain P [auth F] Focus chain S [auth B] Interactions & Density Focus chain H [auth D] Focus chain K [auth A] Focus chain P [auth F] Focus chain S [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
YY3	BindingDB: 7JXP	Ki: min: 2.2, max: 434 (nM) from 6 assay(s)
		IC50: min: 2.00e-3, max: 19 (nM) from 55 assay(s)
		EC50: min: 6, max: 7930 (nM) from 19 assay(s)
JBJ	BindingDB: 7JXP	IC50: min: 0.26, max: 1000 (nM) from 8 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.16 Å
R-Value Free: 0.247
R-Value Work: 0.212
R-Value Observed: 0.214
Space Group: P 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 57.113	α = 70.56
b = 94.741	β = 78.4
c = 95.569	γ = 79.18

Software Package:

Software Name	Purpose
PHENIX	refinement
xia2	data scaling
PDB_EXTRACT	data extraction
xia2	data reduction
PHASER	phasing
Coot	model building

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2021-09-08

Deposition Author(s):

Beyett, T.S.

Eck, M.J.

Funding Organization	Location	Grant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)	United States	5R01CA201049-05
National Institutes of Health/National Cancer Institute (NIH/NCI)	United States	1F32CA247198-01

Revision History (Full details and data files)

Version 1.0: 2021-09-08
Type: Initial release
Version 1.1: 2022-05-18
Changes: Database references
Version 1.2: 2023-10-18
Changes: Data collection, Refinement description
Version 1.3: 2024-10-23
Changes: Structure summary

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Help and Resources

7JXP

EGFR kinase (T790M/V948R) in complex with osimertinib and JBJ-04-125-02

Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)