Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | AEE-788 | Ligand Info | |||
| Canonical SMILES | CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4NC(C)C5=CC=CC=C5 | ||||
| InChI | 1S/C27H32N6/c1-3-32-13-15-33(16-14-32)18-21-9-11-23(12-10-21)25-17-24-26(28-19-29-27(24)31-25)30-20(2)22-7-5-4-6-8-22/h4-12,17,19-20H,3,13-16,18H2,1-2H3,(H2,28,29,30,31)/t20-/m1/s1 | ||||
| InChIKey | OONFNUWBHFSNBT-HXUWFJFHSA-N | ||||
| PubChem Compound ID | 10297043 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 2JIU Crystal structure of EGFR kinase domain T790M mutation in complex with AEE788 | ||||||
| Method | X-ray diffraction | Resolution | 3.05 Å | Mutation | Yes | [1] |
| PDB Sequence |
GEAPNQALLR
705 ILKETEFKKI715 KVLGSGAFGT725 VYKGLWIPEG735 EKVKIPVAIK745 ELREATSPKA 755 NKEILDEAYV765 MASVDNPHVC775 RLLGICLTST785 VQLIMQLMPF795 GCLLDYVREH 805 KDNIGSQYLL815 NWCVQIAKGM825 NYLEDRRLVH835 RDLAARNVLV845 KTPQHVKITD 855 FGLAKLLGAE865 EKEYHAEGGK875 VPIKWMALES885 ILHRIYTHQS895 DVWSYGVTVW 905 ELMTFGSKPY915 DGIPASEISS925 ILEKGERLPQ935 PPICTIDVYM945 IMVKCWMIDA 955 DSRPKFRELI965 IEFSKMARDP975 QRYLVIQGDE985 RMHLPSPVVD1012 ADEY |
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|
|
LEU718
3.503
VAL726
3.797
ALA743
3.429
ILE744
3.896
LYS745
3.334
MET766
4.665
LEU788
3.672
ILE789
4.988
MET790
3.828
GLN791
3.558
LEU792
3.361
|
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| PDB ID: 2ITT Crystal structure of EGFR kinase domain L858R mutation in complex with AEE788 | ||||||
| Method | X-ray diffraction | Resolution | 2.73 Å | Mutation | Yes | [2] |
| PDB Sequence |
EAPNQALLRI
706 LKETEFKKIK716 VLGSGAFGTV726 YKGLWIPEGE736 KVKIPVAIKE746 LREATSPKAN 756 KEILDEAYVM766 ASVDNPHVCR776 LLGICLTSTV786 QLITQLMPFG796 CLLDYVREHK 806 DNIGSQYLLN816 WCVQIAKGMN826 YLEDRRLVHR836 DLAARNVLVK846 TPQHVKITDF 856 GRAKLLGAEE866 VPIKWMALES885 ILHRIYTHQS895 DVWSYGVTVW905 ELMTFGSKPY 915 DGIPASEISS925 ILEKGERLPQ935 PPICTIDVYM945 IMVKCWMIDA955 DSRPKFRELI 965 IEFSKMARDP975 QRYLVIQGDE985 RMHLMDEEDM1007 DDVVDADEYL1017 IP |
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|
|
LEU718
3.810
VAL726
4.140
ALA743
3.665
ILE744
4.168
LYS745
3.576
GLU762
4.641
MET766
3.223
LEU788
3.603
ILE789
4.509
THR790
3.222
GLN791
3.101
|
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| PDB ID: 2ITP Crystal structure of EGFR kinase domain G719S mutation in complex with AEE788 | ||||||
| Method | X-ray diffraction | Resolution | 2.74 Å | Mutation | Yes | [2] |
| PDB Sequence |
EAPNQALLRI
706 LKETEFKKIK716 VLSSGAFGTV726 YKGLWIPEGE736 KVKIPVAIKE746 LREATSPKAN 756 KEILDEAYVM766 ASVDNPHVCR776 LLGICLTSTV786 QLITQLMPFG796 CLLDYVREHK 806 DNIGSQYLLN816 WCVQIAKGMN826 YLEDRRLVHR836 DLAARNVLVK846 TPQHVKITDF 856 GLAKLLGAEE866 KEYHAEGGKV876 PIKWMALESI886 LHRIYTHQSD896 VWSYGVTVWE 906 LMTFGSKPYD916 GIPASEISSI926 LEKGERLPQP936 PICTIDVYMI946 MVKCWMIDAD 956 SRPKFRELII966 EFSKMARDPQ976 RYLVIQGDMD1003 EEDMDDVVDA1013 DEYLI |
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|
|
LEU718
3.874
VAL726
4.038
ALA743
3.664
ILE744
4.122
LYS745
3.490
GLU762
4.690
MET766
3.626
LEU788
3.794
ILE789
4.813
THR790
3.370
GLN791
3.053
|
|||||
| PDB ID: 2J6M Crystal structure of EGFR kinase domain in complex with AEE788 | ||||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | No | [2] |
| PDB Sequence |
EAPNQALLRI
706 LKETEFKKIK716 VLGSGAFGTV726 YKGLWIPEGE736 KVKIPVAIKE746 LREATSPKAN 756 KEILDEAYVM766 ASVDNPHVCR776 LLGICLTSTV786 QLITQLMPFG796 CLLDYVREHK 806 DNIGSQYLLN816 WCVQIAKGMN826 YLEDRRLVHR836 DLAARNVLVK846 TPQHVKITDF 856 GLAKLLGAEE866 KEYHAEGGKV876 PIKWMALESI886 LHRIYTHQSD896 VWSYGVTVWE 906 LMTFGSKPYD916 GIPASEISSI926 LEKGERLPQP936 PICTIDVYMI946 MVKCWMIDAD 956 SRPKFRELII966 EFSKMARDPQ976 RYLVIQGDDE1004 EDMDDVVDAD1014 EYLIPQ |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AEE or .AEE2 or .AEE3 or :3AEE;style chemicals stick;color identity;select .A:718 or .A:726 or .A:743 or .A:744 or .A:745 or .A:762 or .A:766 or .A:788 or .A:789 or .A:790 or .A:791 or .A:792 or .A:793 or .A:794 or .A:795 or .A:796 or .A:797 or .A:800 or .A:804 or .A:844 or .A:854 or .A:855; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU718
4.014
VAL726
4.195
ALA743
3.459
ILE744
4.427
LYS745
4.092
GLU762
3.905
MET766
4.170
LEU788
4.122
ILE789
4.917
THR790
3.022
GLN791
3.470
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5. | ||||
| REF 2 | 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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