Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T66396 | Target Info | |||
| Target Name | Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4) | ||||
| Synonyms | eIF-2-alpha kinase GCN2; KIAA1338; GCN2-like protein; GCN2 | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | EIF2AK4 | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: TKI258 | Ligand Info | |||||
| Structure Description | GCN2 (EIF2ALPHA KINASE 4, E2AK4) IN COMPLEX WITH COMPOUND 1 (dovitinib) | PDB:7QQ6 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [1] |
| PDB Sequence |
SRYFIEFEEL
593 QLLGKGAFGA603 VIKVQNKLDG613 CCYAVKRIPI623 NPASRQFRRI633 KGEVTLLSRL 643 HHENIVRYYN653 AWIERHERPV795 HYLYIQMEYC805 EKSTLRDTID815 QGLYRDTVRL 825 WRLFREILDG835 LAYIHEKGMI845 HRNLKPVNIF855 LDSDDHVKIG865 DFGLIKSDPS 895 GHLTGMVGTA905 LYVSPEVQGS915 TKSAYNQKVD925 LFSLGIIFFE935 MSYHPMVTAS 945 ERIFVLNQLR955 DPTSPKFPED965 FDDGEHAKQK975 SVISWLLNHD985 PAKRPTATEL 995 LKSELLPPP
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| Ligand Name: (2~{S})-~{N}-[(1~{S})-1-[4-[(6-pyridin-4-ylquinazolin-2-yl)amino]phenyl]ethyl]piperidine-2-carboxamide | Ligand Info | |||||
| Structure Description | GCN2 (EIF2ALPHA KINASE 4, E2AK4) IN COMPLEX WITH COMPOUND 2 | PDB:7QWK | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [1] |
| PDB Sequence |
FSRYFIEFEE
592 LQLLGKGAFG602 AVIKVQNKLD612 GCCYAVKRIP622 INPASRQFRR632 IKGEVTLLSR 642 LHHENIVRYY652 NAWIERHVHY797 LYIQMEYCEK807 STLRDTIDQG817 LYRDTVRLWR 827 LFREILDGLA837 YIHEKGMIHR847 NLKPVNIFLD857 SDDHVKIGDF867 GLGTALYVSP 910 EVQGSTYNQK923 VDLFSLGIIF933 FEMSYHPMVT943 ASERIFVLNQ953 LRDPTSPKFP 963 EDFDDGEHAK973 QKSVISWLLN983 HDPAKRPTAT993 ELLKS
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GLN594
3.619
LEU596
3.741
VAL604
3.943
ALA617
3.653
LYS619
3.820
LEU640
4.950
VAL649
3.715
ILE800
4.963
MET802
3.629
GLU803
3.131
TYR804
3.288
|
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| Ligand Name: N-{6-[(1-methyl-2-{[4-(trifluoromethyl)phenyl]amino}-1H-benzimidazol-5-yl)oxy]pyrimidin-4-yl}cyclopropanecarboxamide | Ligand Info | |||||
| Structure Description | Identification of novel, potent and selective GCN2 inhibitors as first-in-class anti-tumor agents | PDB:6N3L | ||||
| Method | X-ray diffraction | Resolution | 2.61 Å | Mutation | Yes | [2] |
| PDB Sequence |
SRYFIEFEEL
593 QLLGKGAFGA603 VIKVQNKLDG613 CCYAVKRIPI623 NPASRQFRRI633 KGEVTLLSRL 643 HHENIVRYYN653 AWIENVHYLY799 IQMEYCEAST809 LRDTIDQGLY819 RDTVRLWRLF 829 REILDGLAYI839 HEKGMIHRNL849 KPVNIFLDSD859 DHVKIGDFAA905 LYVSPEYNQK 923 VDLFSLGIIF933 FEMSYHPMVT943 ASERIFVLNQ953 LRDPFPEDFH971 AKQKSVISWL 981 LNHDPAKRPT991 ATELLKSELL1001 P
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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 .KAV or .KAV2 or .KAV3 or :3KAV;style chemicals stick;color identity;select .A:596 or .A:604 or .A:617 or .A:618 or .A:619 or .A:636 or .A:640 or .A:643 or .A:648 or .A:649 or .A:800 or .A:802 or .A:803 or .A:804 or .A:805 or .A:806 or .A:807 or .A:808 or .A:809 or .A:839 or .A:844 or .A:846 or .A:855 or .A:864 or .A:865 or .A:866 or .A:867; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU596
3.485
VAL604
3.555
ALA617
3.295
VAL618
4.548
LYS619
3.641
GLU636
2.984
LEU640
3.530
LEU643
3.259
ILE648
3.730
VAL649
3.923
ILE800
3.745
MET802
3.545
GLU803
3.162
TYR804
3.484
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| Ligand Name: GCN2iB | Ligand Info | |||||
| Structure Description | Identification of novel, potent and selective GCN2 inhibitors as first-in-class anti-tumor agents | PDB:6N3O | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [2] |
| PDB Sequence |
SRYFIEFEEL
593 QLLGKGAFGA603 VIKVQNKLDG613 CCYAVKRIPI623 NPASRQFRRI633 KGEVTLLSRL 643 HHENIVRYYN653 AWIENAVHYL798 YIQMEYCEAS808 TLRDTIDQGL818 YRDTVRLWRL 828 FREILDGLAY838 IHEKGMIHRN848 LKPVNIFLDS858 DDHVKIGDFG868 LATDHLAFSE 904 ALYVSPEYNQ922 KVDLFSLGII932 FFEMSYHPMV942 TASERIFVLN952 QLRDPTSPKF 962 PEDFDDGEHA972 KQKSVISWLL982 NHDPAKRPTA992 TELLKSELLP1002 PP |
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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 .KA7 or .KA72 or .KA73 or :3KA7;style chemicals stick;color identity;select .A:596 or .A:604 or .A:617 or .A:618 or .A:619 or .A:637 or .A:640 or .A:641 or .A:648 or .A:649 or .A:651 or .A:800 or .A:802 or .A:803 or .A:804 or .A:805 or .A:808 or .A:855 or .A:864 or .A:865 or .A:866 or .A:867 or .A:868 or .A:869; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU596
3.651
VAL604
3.429
ALA617
3.234
VAL618
3.911
LYS619
3.452
VAL637
3.945
LEU640
3.443
SER641
4.178
ILE648
3.485
VAL649
3.492
TYR651
3.593
ILE800
3.788
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| Ligand Name: Gcn2-IN-6 | Ligand Info | |||||
| Structure Description | Identification of novel, potent and selective GCN2 inhibitors as first-in-class anti-tumor agents | PDB:6N3N | ||||
| Method | X-ray diffraction | Resolution | 3.01 Å | Mutation | Yes | [2] |
| PDB Sequence |
SRYFIEFEEL
593 QLLGKGAFGA603 VIKVQNKLDG613 CCYAVKRIPI623 NPASFRRIKG635 EVTLLSRLHH 645 ENIVRYYNAW655 IENVHYLYIQ801 MEYCEASTLR811 DTIDQGLYRD821 TVRLWRLFRE 831 ILDGLAYIHE841 KGMIHRNLKP851 VNIFLDSDDH861 VKIGDFGLAT871 DHLAFEALYV 908 SPEYNQKVDL926 FSLGIIFFEM936 SYHPMVTASE946 RIFVLNQLRD956 PTSPKFPEDH 971 AKQKSVISWL981 LNHDPAKRPT991 ATELLKSELL1001 PP
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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 .KA4 or .KA42 or .KA43 or :3KA4;style chemicals stick;color identity;select .A:596 or .A:604 or .A:617 or .A:618 or .A:619 or .A:637 or .A:640 or .A:641 or .A:643 or .A:648 or .A:649 or .A:651 or .A:800 or .A:802 or .A:803 or .A:804 or .A:805 or .A:808 or .A:855 or .A:864 or .A:865 or .A:866 or .A:867 or .A:868 or .A:869; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU596
3.268
VAL604
3.877
ALA617
3.370
VAL618
3.585
LYS619
3.222
VAL637
4.063
LEU640
2.842
SER641
3.952
LEU643
3.775
ILE648
3.723
VAL649
3.646
TYR651
3.417
ILE800
3.738
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The structure of human GCN2 reveals a parallel, back-to-back kinase dimer with a plastic DFG activation loop motif. Biochem J. 2020 Jan 17;477(1):275-284. | ||||
| REF 2 | Identification of Novel, Potent, and Orally Available GCN2 Inhibitors with Type I Half Binding Mode. ACS Med Chem Lett. 2019 Sep 19;10(10):1498-1503. | ||||
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