Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T59328 Target Info
Target Name Epidermal growth factor receptor (EGFR)
Synonyms Receptor tyrosine-protein kinase erbB-1; Proto-oncogene c-ErbB-1; HER1; ERBB1; ERBB
Target Type Successful Target
Gene Name EGFR
Biochemical Class Kinase
UniProt ID
EGFR_HUMAN
Ligand General Information  Top
Ligand Name AMP-PNP Ligand Info
Canonical SMILES C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(NP(=O)(O)O)O)O)O)N
InChI 1S/C10H17N6O12P3/c11-8-5-9(13-2-12-8)16(3-14-5)10-7(18)6(17)4(27-10)1-26-31(24,25)28-30(22,23)15-29(19,20)21/h2-4,6-7,10,17-18H,1H2,(H,24,25)(H2,11,12,13)(H4,15,19,20,21,22,23)/t4-,6-,7-,10-/m1/s1
InChIKey PVKSNHVPLWYQGJ-KQYNXXCUSA-N
PubChem Compound ID 33113
Drug Binding Sites of Target  Top
PDB ID: 5CNN      Crystal structure of the EGFR kinase domain mutant I682Q
Method X-ray diffraction Resolution 1.90 Å Mutation Yes [1]
PDB Sequence
PNQALLRQLK
684
ETEFKKIKVL
694
GSGAFGTVYK
704
GLWIPEGEKV
714
KIPVAIKELR
724

EAKANKEILD
737
EAYVMASVDN
747
PHVCRLLGIC
757
LTSTVQLITQ
767
LMPFGCLLDY
777

VREHKDNIGS
787
QYLLNWCVQI
797
AKGMNYLEDR
807
RLVHRDLAAR
817
NVLVKTPQHV
827

KITDFGLAKL
837
KVPIKWMALE
860
SILHRIYTHQ
870
SDVWSYGVTV
880
WELMTFGSKP
890

YDGIPASEIS
900
SILEKGERLP
910
QPPICTIDVY
920
MIMVKCWMID
930
ADSRPKFREL
940

IIEFSKMARD
950
PQRYLVIQGD
960
ERMHLPSPTD
970
SNFYRALMDE
980
EDMDDVVDAD
990
Residue
Distance (Å)
LEU694
3.917
GLY695
3.570
SER696
3.381
GLY697
3.338
ALA698
2.666
PHE699
3.792
GLY700
3.437
THR701
4.731
VAL702
3.385
ALA719
3.380
LYS721
2.790
THR766
3.696
Residue
Distance (Å)
GLN767
3.054
LEU768
3.793
MET769
2.975
GLY772
4.478
CYS773
3.693
ASP776
4.274
ASP813
2.425
ARG817
2.910
ASN818
2.718
LEU820
3.549
ASP831
2.735
PDB ID: 3VJN      Crystal structure of the mutated EGFR kinase domain (G719S/T790M) in complex with AMPPNP.
Method X-ray diffraction Resolution 2.34 Å Mutation Yes [2]
PDB Sequence
EAPNQALLRI
706
LKETEFKKIK
716
VLSSGTVYKG
729
LWIPEGEKVK
739
IPVAIKELEA
750

TSPKANKEIL
760
DEAYVMASVD
770
NPHVCRLLGI
780
CLTSTVQLIM
790
QLMPFGCLLD
800

YVREHKDNIG
810
SQYLLNWCVQ
820
IAKGMNYLED
830
RRLVHRDLAA
840
RNVLVKTPQH
850

VKITDFGLAK
860
LLGAEEKEYH
870
AEGGKVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900

GVTVWELMTF
910
GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMVKC
950

WMIDADSRPK
960
FRELIIEFSK
970
MARDPQRYLV
980
IQGDDMDDVV
1011
DADEYLI
Residue
Distance (Å)
LEU718
4.065
SER719
3.529
VAL726
3.803
ALA743
3.425
LYS745
3.030
CYS775
4.900
MET790
3.157
GLN791
2.959
Residue
Distance (Å)
LEU792
3.904
MET793
2.953
GLY796
4.730
CYS797
3.799
ARG841
4.917
ASN842
4.434
LEU844
3.625
ASP855
3.199
PDB ID: 3VJO      Crystal structure of the wild-type EGFR kinase domain in complex with AMPPNP.
Method X-ray diffraction Resolution 2.64 Å Mutation No [2]
PDB Sequence
GEAPNQALLR
705
ILKETEFKKI
715
KVLGSFGTVY
727
KGLWIPEGEK
737
VKIPVAIKEA
750

TSPKANKEIL
760
DEAYVMASVD
770
NPHVCRLLGI
780
CLTSTVQLIT
790
QLMPFGCLLD
800

YVREHKDNIG
810
SQYLLNWCVQ
820
IAKGMNYLED
830
RRLVHRDLAA
840
RNVLVKTPQH
850

VKITDFGLAK
860
LLGAEEKEYH
870
AEGGKVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900

GVTVWELMTF
910
GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMVKC
950

WMIDADSRPK
960
FRELIIEFSK
970
MARDPQRYLV
980
IQGDEDMDDV
1010
VDADEYLI
Residue
Distance (Å)
LEU718
3.913
GLY719
4.020
PHE723
3.645
VAL726
4.052
ALA743
3.178
LYS745
3.037
THR790
3.598
GLN791
3.043
Residue
Distance (Å)
LEU792
3.729
MET793
2.951
PRO794
4.859
GLY796
4.536
CYS797
3.787
LEU844
3.909
ASP855
3.966
PDB ID: 2EB3      Crystal structure of mutated EGFR kinase domain (L858R) in complex with AMPPNP
Method X-ray diffraction Resolution 2.84 Å Mutation No [2]
PDB Sequence
GEAPNQALLR
705
ILKETEFKKI
715
KVLGSAFGTV
726
YKGLWIPEGE
736
KVKIPVAIKE
746

LREATSPKAN
756
KEILDEAYVM
766
ASVDNPHVCR
776
LLGICLTSTV
786
QLITQLMPFG
796

CLLDYVREHK
806
DNIGSQYLLN
816
WCVQIAKGMN
826
YLEDRRLVHR
836
DLAARNVLVK
846

TPQHVKITDF
856
GRAKLVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900
GVTVWELMTF
910

GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMVKC
950
WMIDADSRPK
960

FRELIIEFSK
970
MARDPQRYLV
980
IQGDERMHLP
990
EDMDDVVDAD
1014
EYLI
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:722 or .A:724 or .A:726 or .A:743 or .A:745 or .A:758 or .A:762 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:796 or .A:797 or .A:841 or .A:842 or .A:844 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.846
GLY719
3.933
SER720
4.535
ALA722
4.027
GLY724
4.394
VAL726
3.298
ALA743
3.439
LYS745
2.771
GLU758
4.546
GLU762
4.515
THR790
3.598
Residue
Distance (Å)
GLN791
3.223
LEU792
3.791
MET793
3.180
PRO794
4.980
GLY796
4.613
CYS797
4.019
ARG841
4.945
ASN842
4.292
LEU844
3.581
ASP855
2.505
PDB ID: 7JXQ      EGFR kinase (T790M/V948R) in complex with allosteric inhibitor JBJ-09-063
Method X-ray diffraction Resolution 1.83 Å Mutation Yes [3]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
MQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGLA
859
KLLGAEVPIK
879
WMALESILHR
889
IYTHQSDVWS
899
YGVTVWELMT
909

FGSKPYDGIP
919
ASEISSILEK
929
GERLPQPPIC
939
TIDVYMIMRK
949
CWMIDADSRP
959

KFRELIIEFS
969
KMARDPQRYL
979
VIQGDERMHL
989
PSPTDSNFYR
999
ALMDEEDM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.794
GLY719
3.569
SER720
3.529
GLY721
3.020
ALA722
3.124
PHE723
4.621
GLY724
3.935
VAL726
3.401
ALA743
3.484
LYS745
2.711
MET790
3.409
Residue
Distance (Å)
GLN791
2.883
LEU792
3.852
MET793
2.934
GLY796
4.544
CYS797
3.277
ASP800
4.526
ASP837
2.578
ARG841
2.857
ASN842
3.033
LEU844
3.511
ASP855
2.748
PDB ID: 5X2A      Crystal structure of EGFR 696-1022 T790M/V948R in complex with SKLB(3)
Method X-ray diffraction Resolution 1.85 Å Mutation Yes [4]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
MQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGLA
859
KLLVPIKWMA
882
LESILHRIYT
892
HQSDVWSYGV
902
TVWELMTFGS
912

KPYDGIPASE
922
ISSILEKGER
932
LPQPPICTID
942
VYMIMRKCWM
952
IDADSRPKFR
962

ELIIEFSKMA
972
RDPQRYLVIQ
982
GDERMHLPSP
992
TDSNFYRALM
1002
DEEDMVV
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:726 or .A:745 or .A:837 or .A:841 or .A:842 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
4.968
GLY719
3.585
SER720
3.430
GLY721
3.176
ALA722
2.948
PHE723
3.882
GLY724
3.769
Residue
Distance (Å)
VAL726
3.068
LYS745
2.980
ASP837
2.484
ARG841
2.758
ASN842
2.692
ASP855
2.369
PDB ID: 4ZSE      Crystal structure of EGFR 696-1022 T790M/V948R, crystal form II
Method X-ray diffraction Resolution 1.97 Å Mutation Yes [5]
PDB Sequence
PNQALLRILK
708
ETEFKKIKVL
718
GSGAFGTVYK
728
GLWIPEGEKV
738
KIPVAIKELR
748

EATSPKANKE
758
ILDEAYVMAS
768
VDNPHVCRLL
778
GICLTSTVQL
788
IMQLMPFGCL
798

LDYVREHKDN
808
IGSQYLLNWC
818
VQIAKGMNYL
828
EDRRLVHRDL
838
AARNVLVKTP
848

QHVKITDFGL
858
AKLLKVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900
GVTVWELMTF
910

GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMRKC
950
WMIDADSRPK
960

FRELIIEFSK
970
MARDPQRYLV
980
IQGDERMHLP
990
SPTDSNFYRA
1000
LMDEEDM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:725 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.497
GLY719
3.647
SER720
3.653
GLY721
3.159
ALA722
3.111
PHE723
4.221
GLY724
3.433
THR725
4.902
VAL726
3.330
ALA743
3.529
LYS745
2.912
MET790
3.937
Residue
Distance (Å)
GLN791
3.057
LEU792
3.833
MET793
2.955
GLY796
4.633
CYS797
3.467
ASP800
4.607
ASP837
2.648
ARG841
2.879
ASN842
2.960
LEU844
3.448
ASP855
2.745
PDB ID: 7JXP      EGFR kinase (T790M/V948R) in complex with osimertinib and JBJ-04-125-02
Method X-ray diffraction Resolution 2.16 Å Mutation Yes [6]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
MQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGLA
859
KLVPIKWMAL
883
ESILHRIYTH
893
QSDVWSYGVT
903
VWELMTFGSK
913

PYDGIPASEI
923
SSILEKGERL
933
PQPPICTIDV
943
YMIMRKCWMI
953
DADSRPKFRE
963

LIIEFSKMAR
973
DPQRYLVIQG
983
DERMHLPSPT
993
DSNFYRALMD
1003
EEDM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:725 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.704
GLY719
3.437
SER720
3.631
GLY721
3.208
ALA722
2.714
PHE723
4.762
GLY724
3.673
THR725
4.804
VAL726
3.158
ALA743
3.561
LYS745
3.178
MET790
3.439
Residue
Distance (Å)
GLN791
3.019
LEU792
3.758
MET793
3.119
GLY796
4.601
CYS797
3.152
ASP800
4.074
ASP837
2.536
ARG841
2.665
ASN842
2.782
LEU844
3.325
ASP855
2.629
PDB ID: 7JXM      EGFR kinase (T790M/V948R) in complex with osimertinib and EAI045
Method X-ray diffraction Resolution 2.19 Å Mutation Yes [6]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
MQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGLV
876
PIKWMALESI
886
LHRIYTHQSD
896
VWSYGVTVWE
906
LMTFGSKPYD
916

GIPASEISSI
926
LEKGERLPQP
936
PICTIDVYMI
946
MRKCWMIDAD
956
SRPKFRELII
966

EFSKMARDPQ
976
RYLVIQGDER
986
MHLPSPTDSN
996
FYRALMDEED
1006
M
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.779
GLY719
3.693
SER720
3.456
GLY721
3.061
ALA722
2.985
PHE723
4.900
GLY724
3.498
VAL726
3.350
ALA743
3.545
LYS745
3.365
MET790
3.280
Residue
Distance (Å)
GLN791
3.030
LEU792
3.869
MET793
3.019
GLY796
4.397
CYS797
3.361
ASP800
4.284
ASP837
2.645
ARG841
2.559
ASN842
3.143
LEU844
3.381
ASP855
2.757
PDB ID: 6DUK      EGFR with an allosteric inhibitor
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [7]
PDB Sequence
QALLRILKET
710
EFKKIKVLGS
720
GAFGTVYKGL
730
WIPEGEKVKI
740
PVAIKELREA
750

TSPKANKEIL
760
DEAYVMASVD
770
NPHVCRLLGI
780
CLTSTVQLIM
790
QLMPFGCLLD
800

YVREHKDNIG
810
SQYLLNWCVQ
820
IAKGMNYLED
830
RRLVHRDLAA
840
RNVLVKTPQH
850

VKITDFGLAK
860
LLGAEEKEYH
870
AEGGKVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900

GVTVWELMTF
910
GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMRKC
950

WMIDADSRPK
960
FRELIIEFSK
970
MARDPQRYLV
980
IQGDERMHLP
990
SPTDSNFYRA
1000

LMDEED
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:725 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.888
GLY719
3.517
SER720
3.485
GLY721
3.437
ALA722
2.818
PHE723
4.627
GLY724
3.366
THR725
4.469
VAL726
3.408
ALA743
3.541
LYS745
2.767
MET790
3.327
Residue
Distance (Å)
GLN791
3.019
LEU792
3.659
MET793
2.976
GLY796
4.479
CYS797
3.631
ASP800
3.577
ASP837
2.648
ARG841
2.904
ASN842
2.866
LEU844
3.395
ASP855
2.889
PDB ID: 7LTX      EGFR (T790M/V948R) in complex with quinazolinone allosteric inhibitor
Method X-ray diffraction Resolution 2.30 Å Mutation Yes [8]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
MQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGLA
859
VPIKWMALES
885
ILHRIYTHQS
895
DVWSYGVTVW
905
ELMTFGSKPY
915

DGIPASEISS
925
ILEKGERLPQ
935
PPICTIDVYM
945
IMRKCWMIDA
955
DSRPKFRELI
965

IEFSKMARDP
975
QRYLVIQGDE
985
RMHLPSPTDS
995
NFYRALMDEE
1005
DM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:725 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.798
GLY719
3.698
SER720
3.575
GLY721
3.285
ALA722
3.200
PHE723
4.488
GLY724
3.600
THR725
4.882
VAL726
3.400
ALA743
3.488
LYS745
2.828
MET790
3.503
Residue
Distance (Å)
GLN791
2.865
LEU792
3.849
MET793
3.029
GLY796
4.432
CYS797
3.200
ASP800
4.068
ASP837
2.648
ARG841
2.930
ASN842
2.842
LEU844
3.625
ASP855
2.846
PDB ID: 5D41      EGFR kinase domain in complex with mutant selective allosteric inhibitor
Method X-ray diffraction Resolution 2.31 Å Mutation Yes [9]
PDB Sequence
APNQALLRIL
707
KETEFKKIKV
717
LGSGAFGTVY
727
KGLWIPEGEK
737
VKIPVAIKEL
747

REATSPKANK
757
EILDEAYVMA
767
SVDNPHVCRL
777
LGICLTSTVQ
787
LIMQLMPFGC
797

LLDYVREHKD
807
NIGSQYLLNW
817
CVQIAKGMNY
827
LEDRRLVHRD
837
LAARNVLVKT
847

PQHVKITDFG
857
LVPIKWMALE
884
SILHRIYTHQ
894
SDVWSYGVTV
904
WELMTFGSKP
914

YDGIPASEIS
924
SILEKGERLP
934
QPPICTIDVY
944
MIMRKCWMID
954
ADSRPKFREL
964

IIEFSKMARD
974
PQRYLVIQGD
984
ERMHLPSPTD
994
SNFYRALMDE
1004
EDMDDVVDAD
1014
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:725 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.826
GLY719
3.724
SER720
3.434
GLY721
3.259
ALA722
2.883
PHE723
3.783
GLY724
3.631
THR725
4.677
VAL726
3.213
ALA743
3.383
LYS745
2.701
MET790
3.425
Residue
Distance (Å)
GLN791
2.910
LEU792
3.891
MET793
3.053
GLY796
4.288
CYS797
3.575
ASP800
3.804
ASP837
2.617
ARG841
2.888
ASN842
2.911
LEU844
3.396
ASP855
2.781
PDB ID: 7JXK      EGFR kinase (T790M/V948R) in complex with PF-06747775 and JBJ-04-125-02
Method X-ray diffraction Resolution 3.10 Å Mutation Yes [6]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
MQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGLA
859
KLVPIKWMAL
883
ESILHRIYTH
893
QSDVWSYGVT
903
VWELMTFGSK
913

PYDGIPASEI
923
SSILEKGERL
933
PQPPICTIDV
943
YMIMRKCWMI
953
DADSRPKFRE
963

LIIEFSKMAR
973
DPQRYLVIQG
983
DERMHLPSPT
993
DSNFYRALMD
1003
EEDM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
4.034
GLY719
3.380
SER720
3.454
GLY721
3.210
ALA722
4.122
PHE723
3.571
GLY724
3.313
VAL726
3.145
ALA743
3.272
LYS745
3.100
MET790
3.787
Residue
Distance (Å)
GLN791
2.923
LEU792
3.763
MET793
3.257
GLY796
4.602
CYS797
3.186
ASP800
4.391
ASP837
3.054
ARG841
2.253
ASN842
2.413
LEU844
3.753
ASP855
3.005
PDB ID: 7K1I      EGFR kinase (L858R/V948R) in complex with allosteric inhibitor JBJ-09-063
Method X-ray diffraction Resolution 3.20 Å Mutation Yes [6]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
TQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGRV
876
PIKWMALESI
886
IYTHQSDVWS
899
YGVTVWELMT
909
FGSKPYDGIP
919

ASEISSILEK
929
GERLPQPPIC
939
TIDVYMIMRK
949
CWMIDADSRP
959
KFRELIIEFS
969

KMARDPQRYL
979
VIQGDERMHL
989
PSPTDSNFYR
999
ALMDEEDM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:854 or .A:855 or .A:858; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.931
GLY719
3.602
SER720
3.691
GLY721
3.331
ALA722
4.407
PHE723
3.585
GLY724
4.242
VAL726
3.385
ALA743
3.732
LYS745
2.847
THR790
3.860
GLN791
2.786
Residue
Distance (Å)
LEU792
3.764
MET793
2.817
GLY796
4.334
CYS797
3.129
ASP800
4.246
ASP837
2.514
ARG841
3.038
ASN842
2.693
LEU844
3.221
THR854
4.879
ASP855
2.724
ARG858
3.176
PDB ID: 5CNO      Crystal structure of the EGFR kinase domain mutant V924R
Method X-ray diffraction Resolution 1.55 Å Mutation Yes [1]
PDB Sequence
NQALLRILKE
685
TEFKKIKVLG
695
SGAFGTVYKG
705
LWIPEGEKVK
715
IPVAIKELRE
725

ANKEILDEAY
740
VMASVDNPHV
750
CRLLGICLTS
760
TVQLITQLMP
770
FGCLLDYVRE
780

HKDNIGSQYL
790
LNWCVQIAKG
800
MNYLEDRRLV
810
HRDLAARNVL
820
VKTPQHVKIT
830

DFGLAKLLGK
851
VPIKWMALES
861
ILHRIYTHQS
871
DVWSYGVTVW
881
ELMTFGSKPY
891

DGIPASEISS
901
ILEKGERLPQ
911
PPICTIDVYM
921
IMRKCWMIDA
931
DSRPKFRELI
941

IEFSKMARDP
951
QRYLVIQGDE
961
RMHLPSPTDS
971
NFYRALMDEE
981
DMDDVVDADE
991
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:694 or .A:695 or .A:696 or .A:697 or .A:698 or .A:699 or .A:700 or .A:701 or .A:702 or .A:719 or .A:721 or .A:766 or .A:767 or .A:768 or .A:769 or .A:772 or .A:773 or .A:776 or .A:813 or .A:817 or .A:818 or .A:820 or .A:830 or .A:831; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU694
3.654
GLY695
3.450
SER696
3.597
GLY697
3.190
ALA698
2.924
PHE699
4.094
GLY700
3.438
THR701
4.799
VAL702
3.443
ALA719
3.498
LYS721
2.714
THR766
3.736
Residue
Distance (Å)
GLN767
2.917
LEU768
3.822
MET769
2.996
GLY772
4.798
CYS773
3.627
ASP776
4.927
ASP813
2.533
ARG817
2.894
ASN818
2.924
LEU820
3.519
THR830
4.739
ASP831
2.835
PDB ID: 2GS7      Crystal Structure of the inactive EGFR kinase domain in complex with AMP-PNP
Method X-ray diffraction Resolution 2.60 Å Mutation Yes [10]
PDB Sequence
LLRILKETEF
688
KKIKVLGSGA
698
FGTVYKGLWI
708
PEGEKVKIPV
718
AIKELREATS
728

PKANKEILDE
738
AYVMASVDNP
748
HVCRLLGICL
758
TSTVQLITQL
768
MPFGCLLDYV
778

REHKDNIGSQ
788
YLLNWCVQIA
798
KGMNYLEDRR
808
LVHRDLAARN
818
VLVKTPQHVK
828

ITDFGLAKLL
838
GAEEKEYHKV
852
PIKWMALESI
862
LHRIYTHQSD
872
VWSYGVTVWE
882

LMTFGSKPYD
892
GIPASEISSI
902
LEKGERLPQP
912
PICTIDVYMI
922
MRKCWMIDAD
932

SRPKFRELII
942
EFSKMARDPQ
952
RYLVIQGDVV
987
D
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:694 or .A:695 or .A:696 or .A:697 or .A:698 or .A:702 or .A:719 or .A:721 or .A:766 or .A:767 or .A:768 or .A:769 or .A:772 or .A:773 or .A:776 or .A:817 or .A:818 or .A:820 or .A:830 or .A:831; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU694
3.119
GLY695
3.447
SER696
4.956
GLY697
3.651
ALA698
4.853
VAL702
3.479
ALA719
3.604
LYS721
2.630
THR766
3.519
GLN767
3.333
Residue
Distance (Å)
LEU768
4.126
MET769
3.091
GLY772
4.774
CYS773
4.080
ASP776
4.800
ARG817
3.119
ASN818
4.227
LEU820
3.532
THR830
4.632
ASP831
3.238
PDB ID: 3GT8      Crystal structure of the inactive EGFR kinase domain in complex with AMP-PNP
Method X-ray diffraction Resolution 2.96 Å Mutation Yes [11]
PDB Sequence
QALLRILKET
686
EFKKIKVLGS
696
GAFGTVYKGL
706
WIPEGEKVKI
716
PVAIKELREA
726

TSPKANKEIL
736
DEAYVMASVD
746
NPHVCRLLGI
756
CLTSTVQLIT
766
QLMPFGCLLD
776

YVREHKDNIG
786
SQYLLNWCVQ
796
IAKGMNYLED
806
RRLVHRDLAA
816
RNVLVKTPQH
826

VKITDFGLAK
836
LPIKWMALES
861
ILHRIYTHQS
871
DVWSYGVTVW
881
ELMTFGSKPY
891

DGIPASEISS
901
ILEKGERLPQ
911
PPICTIDVYM
921
IMRKCWMIDA
931
DSRPKFRELI
941

IEFSKMARDP
951
QRYLVIQGDE
961
RMHLPSPTDS
971
NFYRALMDEE
981
DM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:694 or .B:695 or .B:696 or .B:697 or .B:698 or .B:699 or .B:700 or .B:701 or .B:702 or .B:719 or .B:721 or .B:766 or .B:767 or .B:768 or .B:769 or .B:770 or .B:772 or .B:773 or .B:776 or .B:813 or .B:817 or .B:818 or .B:820 or .B:830 or .B:831; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU694
4.069
GLY695
3.718
SER696
3.169
GLY697
3.059
ALA698
2.973
PHE699
3.124
GLY700
3.084
THR701
4.475
VAL702
3.126
ALA719
3.633
LYS721
2.335
THR766
3.929
GLN767
2.626
Residue
Distance (Å)
LEU768
3.523
MET769
2.551
PRO770
4.894
GLY772
4.398
CYS773
3.847
ASP776
4.377
ASP813
2.926
ARG817
2.644
ASN818
2.900
LEU820
3.296
THR830
4.813
ASP831
3.002
PDB ID: 6WAK      A crystal structure of EGFR(T790M/V948R) in complex with LN3754
Method X-ray diffraction Resolution 2.40 Å Mutation Yes [12]
PDB Sequence
QALLRILKET
710
EFKKIKVLGS
720
GAFGTVYKGL
730
WIPEGEKVKI
740
PVAIKELREA
750

KANKEILDEA
763
YVMASVDNPH
773
VCRLLGICLT
783
STVQLIMQLM
793
PFGCLLDYVR
803

EHKDNIGSQY
813
LLNWCVQIAK
823
GMNYLEDRRL
833
VHRDLAARNV
843
LVKTPQHVKI
853

TDFGLAKLVP
877
IKWMALESIL
887
HRIYTHQSDV
897
WSYGVTVWEL
907
MTFGSKPYDG
917

IPASEISSIL
927
EKGERLPQPP
937
ICTIDVYMIM
947
RKCWMIDADS
957
RPKFRELIIE
967

FSKMARDPQR
977
YLVIQGDERM
987
HLPSPTDSNF
997
YRALMDEEDM
1007
DDVVDAD
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:725 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:854 or .D:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.460
GLY719
3.570
SER720
3.593
GLY721
3.432
ALA722
3.176
PHE723
3.581
GLY724
3.658
THR725
4.870
VAL726
3.387
ALA743
3.365
LYS745
2.817
MET790
3.950
Residue
Distance (Å)
GLN791
3.078
LEU792
3.945
MET793
3.276
GLY796
4.496
CYS797
3.226
ASP800
4.367
ASP837
2.806
ARG841
3.086
ASN842
2.892
LEU844
3.549
THR854
4.822
ASP855
2.838
PDB ID: 6P8Q      EGFR in complex with a dihydrodibenzodiazepinone allosteric inhibitor.
Method X-ray diffraction Resolution 1.90 Å Mutation Yes [13]
PDB Sequence
PNQALLRILK
708
ETEFKKIKVL
718
GSGAFGTVYK
728
GLWIPEGEKV
738
KIPVAIKELR
748

EATSPKANKE
758
ILDEAYVMAS
768
VDNPHVCRLL
778
GICLTSTVQL
788
IMQLMPFGCL
798

LDYVREHKDN
808
IGSQYLLNWC
818
VQIAKGMNYL
828
EDRRLVHRDL
838
AARNVLVKTP
848

QHVKITDFGL
858
AKLLGVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900
GVTVWELMTF
910

GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMRKC
950
WMIDADSRPK
960

FRELIIEFSK
970
MARDPQRYLV
980
IQGDERMHLP
990
SPTDSNFYRA
1000
LMDEEDMDDV
1010

VDADEYLIP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.494
GLY719
3.637
SER720
3.698
GLY721
3.112
ALA722
2.970
PHE723
4.762
GLY724
4.036
VAL726
3.513
ALA743
3.521
LYS745
3.661
MET790
3.271
Residue
Distance (Å)
GLN791
2.876
LEU792
3.827
MET793
2.996
GLY796
4.576
CYS797
3.474
ASP800
4.468
ASP837
2.663
ARG841
2.804
ASN842
2.837
LEU844
3.543
ASP855
2.682
PDB ID: 6P1D      Crystal structure of EGFR with mutant-selective dihydrodibenzodiazepinone allosteric inhibitor
Method X-ray diffraction Resolution 2.40 Å Mutation No [13]
PDB Sequence
QALLRILKET
710
EFKKIKVLGS
720
GAFGTVYKGL
730
WIPEGEKVKI
740
PVAIKELREA
750

TSPKANKEIL
760
DEAYVMASVD
770
NPHVCRLLGI
780
CLTSTVQLIM
790
QLMPFGCLLD
800

YVREHKDNIG
810
SQYLLNWCVQ
820
IAKGMNYLED
830
RRLVHRDLAA
840
RNVLVKTPQH
850

VKITDFGLAK
860
LLVPIKWMAL
883
ESILHRIYTH
893
QSDVWSYGVT
903
VWELMTFGSK
913

PYDGIPASEI
923
SSILEKGERL
933
PQPPICTIDV
943
YMIMRKCWMI
953
DADSRPKFRE
963

LIIEFSKMAR
973
DPQRYLVIQG
983
DERMHLPSPT
993
DSNFYRALMD
1003
EEDMD
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .D:718 or .D:719 or .D:720 or .D:721 or .D:722 or .D:723 or .D:724 or .D:726 or .D:743 or .D:745 or .D:790 or .D:791 or .D:792 or .D:793 or .D:796 or .D:797 or .D:800 or .D:837 or .D:841 or .D:842 or .D:844 or .D:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.556
GLY719
3.540
SER720
3.781
GLY721
3.278
ALA722
2.941
PHE723
3.468
GLY724
3.687
VAL726
3.439
ALA743
3.414
LYS745
3.031
MET790
3.249
Residue
Distance (Å)
GLN791
2.942
LEU792
3.802
MET793
2.907
GLY796
4.480
CYS797
3.226
ASP800
4.297
ASP837
2.318
ARG841
3.048
ASN842
2.960
LEU844
3.556
ASP855
2.752
PDB ID: 2ITN      Crystal structure of EGFR kinase domain G719S mutation in complex with AMP-PNP
Method X-ray diffraction Resolution 2.47 Å Mutation Yes [14]
PDB Sequence
GEAPNQALLR
705
ILKETEFKKI
715
KVLSSGAFGT
725
VYKGLWIPEG
735
EKVKIPVAIK
745

ELREATSPKA
755
NKEILDEAYV
765
MASVDNPHVC
775
RLLGICLTST
785
VQLITQLMPF
795

GCLLDYVREH
805
KDNIGSQYLL
815
NWCVQIAKGM
825
NYLEDRRLVH
835
RDLAARNVLV
845

KTPQHVKITD
855
FGLAKLLGAE
865
EVPIKWMALE
884
SILHRIYTHQ
894
SDVWSYGVTV
904

WELMTFGSKP
914
YDGIPASEIS
924
SILEKGERLP
934
QPPICTIDVY
944
MIMVKCWMID
954

ADSRPKFREL
964
IIEFSKMARD
974
PQRYLVIQGD
984
ERMHLLMDEE
1005
DMDDVVDADE
1015

YLIP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:854 or .A:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.649
SER719
3.377
VAL726
3.911
ALA743
3.395
LYS745
3.209
THR790
3.168
GLN791
2.815
LEU792
3.662
MET793
2.732
PRO794
4.789
Residue
Distance (Å)
GLY796
4.579
CYS797
3.506
ASP800
4.607
ASP837
4.614
ARG841
4.662
ASN842
3.803
LEU844
3.672
THR854
4.901
ASP855
2.253
PDB ID: 2ITV      Crystal structure of EGFR kinase domain L858R mutation in complex with AMP-PNP
Method X-ray diffraction Resolution 2.47 Å Mutation Yes [14]
PDB Sequence
GEAPNQALLR
705
ILKETEFKKI
715
KVLGSGAFGT
725
VYKGLWIPEG
735
EKVKIPVAIK
745

ELREATSPKA
755
NKEILDEAYV
765
MASVDNPHVC
775
RLLGICLTST
785
VQLITQLMPF
795

GCLLDYVREH
805
KDNIGSQYLL
815
NWCVQIAKGM
825
NYLEDRRLVH
835
RDLAARNVLV
845

KTPQHVKITD
855
FGRAKLLGAE
865
EVPIKWMALE
884
SILHRIYTHQ
894
SDVWSYGVTV
904

WELMTFGSKP
914
YDGIPASEIS
924
SILEKGERLP
934
QPPICTIDVY
944
MIMVKCWMID
954

ADSRPKFREL
964
IIEFSKMARD
974
PQRYLVIQGD
984
ERMHLMDEED
1006
MDDVVDADEY
1016

LIP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:722 or .A:723 or .A:724 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.718
GLY719
4.547
ALA722
4.069
PHE723
4.243
GLY724
4.536
VAL726
3.830
ALA743
3.366
LYS745
3.370
THR790
3.148
GLN791
2.820
LEU792
3.579
Residue
Distance (Å)
MET793
2.628
PRO794
4.655
GLY796
4.564
CYS797
3.675
ASP800
4.683
ASP837
4.558
ARG841
4.666
ASN842
3.463
LEU844
3.754
ASP855
2.307
PDB ID: 6P1L      Crystal structure of EGFR in complex with EAI045
Method X-ray diffraction Resolution 2.80 Å Mutation Yes [13]
PDB Sequence
QALLRILKET
710
EFKKIKVLGS
720
GAFGTVYKGL
730
WIPEGEKVKI
740
PVAIKELREA
750

PKANKEILDE
762
AYVMASVDNP
772
HVCRLLGICL
782
TSTVQLIMQL
792
MPFGCLLDYV
802

REHKDNIGSQ
812
YLLNWCVQIA
822
KGMNYLEDRR
832
LVHRDLAARN
842
VLVKTPQHVK
852

ITDFGLVPIK
879
WMALESILHR
889
IYTHQSDVWS
899
YGVTVWELMT
909
FGSKPYDGIP
919

ASEISSILEK
929
GERLPQPPIC
939
TIDVYMIMRK
949
CWMIDADSRP
959
KFRELIIEFS
969

KMARDPQRYL
979
VIQGDERMHL
989
PSPTDSNFYR
999
ALMDEEDM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:720 or .A:721 or .A:722 or .A:723 or .A:724 or .A:725 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
3.687
GLY719
3.794
SER720
3.606
GLY721
3.118
ALA722
2.625
PHE723
4.582
GLY724
3.633
THR725
4.956
VAL726
3.334
ALA743
3.562
LYS745
3.003
MET790
3.276
Residue
Distance (Å)
GLN791
3.057
LEU792
3.840
MET793
2.892
GLY796
4.359
CYS797
3.887
ASP800
4.153
ASP837
2.719
ARG841
2.861
ASN842
2.745
LEU844
3.421
ASP855
2.700
PDB ID: 2ITX      Crystal structure of EGFR kinase domain in complex with AMP-PNP
Method X-ray diffraction Resolution 2.98 Å Mutation No [14]
PDB Sequence
EAPNQALLRI
706
LKETEFKKIK
716
VLGSGAFGTV
726
YKGLWIPEGE
736
KVKIPVAIKE
746

LREATSPKAN
756
KEILDEAYVM
766
ASVDNPHVCR
776
LLGICLTSTV
786
QLITQLMPFG
796

CLLDYVREHK
806
DNIGSQYLLN
816
WCVQIAKGMN
826
YLEDRRLVHR
836
DLAARNVLVK
846

TPQHVKITDF
856
GLAKLEKEYH
870
AEGGKVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900

GVTVWELMTF
910
GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMVKC
950

WMIDADSRPK
960
FRELIIEFSK
970
MARDPQRYLV
980
IQGDERMHLM
1002
DEEDMDDVVD
1012

ADEYLIP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:718 or .A:719 or .A:722 or .A:723 or .A:724 or .A:726 or .A:743 or .A:745 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:796 or .A:797 or .A:800 or .A:837 or .A:841 or .A:842 or .A:844 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU718
4.151
GLY719
4.275
ALA722
3.313
PHE723
4.441
GLY724
4.993
VAL726
3.736
ALA743
3.327
LYS745
3.811
THR790
3.131
GLN791
2.960
LEU792
3.675
Residue
Distance (Å)
MET793
2.681
PRO794
4.716
GLY796
4.014
CYS797
3.654
ASP800
4.730
ASP837
4.600
ARG841
4.374
ASN842
2.901
LEU844
3.528
ASP855
2.519
References  Top
REF 1 Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor. Mol Cell Biol. 2015 Sep 1;35(17):3083-102.
REF 2 Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor. Oncogene. 2013 Jan 3;32(1):27-38.
REF 3 An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer. Nat Cancer. 2022 Apr;3(4):402-417.
REF 4 Structural insights into drug development strategy targeting EGFR T790M/C797S. Oncotarget. 2018 Jan 10;9(17):13652-13665.
REF 5 Ibrutinib Selectively and Irreversibly Targets EGFR-mutant non-Small Cell Lung Cancer Cells
REF 6 Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors. doi:10.1038/s41467-022-30258-y.
REF 7 Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov. 2019 Jul;9(7):926-943.
REF 8 Quinazolinones as allosteric fourth-generation EGFR inhibitors for the treatment of NSCLC. Bioorg Med Chem Lett. 2022 Jul 15;68:128718.
REF 9 Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016 Jun 2;534(7605):129-32.
REF 10 An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell. 2006 Jun 16;125(6):1137-49.
REF 11 Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment. Cell. 2009 Jun 26;137(7):1293-307.
REF 12 Design of a "Two-in-One" Mutant-Selective Epidermal Growth Factor Receptor Inhibitor That Spans the Orthosteric and Allosteric Sites. J Med Chem. 2022 Jan 27;65(2):1370-1383.
REF 13 Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors. ACS Med Chem Lett. 2019 Oct 22;10(11):1549-1553.
REF 14 Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell. 2007 Mar;11(3):217-27.

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