Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T58454 | Target Info | |||
| Target Name | Fibroblast growth factor receptor 2 (FGFR2) | ||||
| Synonyms | Keratinocyte growth factor receptor 2; Keratinocyte growth factor receptor; KSAM; KGFR; K-sam; FGFR-2; FGF-2 receptor; CD332; BEK | ||||
| Target Type | Successful Target | ||||
| Gene Name | FGFR2 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: L-betagamma-meATP | Ligand Info | |||||
| Structure Description | Crystal Structure of Tyrosine Phosphorylated Activated FGF Receptor 2 (FGFR2) Kinase Domain in Complex with ATP Analog and Substrate Peptide | PDB:2PVF | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [1] |
| PDB Sequence |
ELPEDPKWEF
476 PRDKLTLGKP486 LGEGAFGQVV496 MAEAVGIDKD506 KPVTVAVKML519 KDDATEKDLS 529 DLVSEMEMMK539 MIGKHKNIIN549 LLGACTQDGP559 LYVIVEYASK569 GNLREYLRAR 579 RPPGMESYQM598 TFKDLVSCTY608 QLARGMEYLA618 SQKCIHRDLA628 ARNVLVTENN 638 VMKIADFGLA648 RDINNIDKKT660 TNGRLPVKWM670 APEALFDRVY680 THQSDVWSFG 690 VLMWEIFTLG700 GSPYPGIPVE710 ELFKLLKEGH720 RMDKPANCTN730 ELYMMMRDCW 740 HAVPSQRPTF750 KQLVEDLDRI760 LTLTT
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LEU487
3.596
GLY488
3.529
GLU489
4.775
GLY490
2.957
ALA491
3.172
PHE492
3.007
GLY493
2.971
VAL495
3.641
ALA515
3.269
LYS517
2.715
GLU534
4.836
ILE548
4.418
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Phosphonotyrosine | Ligand Info | |||||
| Structure Description | Crystal Structure of Tyrosine Phosphorylated Activated FGF Receptor 2 (FGFR2) Kinase Domain in Complex with ATP Analog and Substrate Peptide | PDB:2PVF | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [1] |
| PDB Sequence |
ELPEDPKWEF
476 PRDKLTLGKP486 LGEGAFGQVV496 MAEAVGIDKD506 KPVTVAVKML519 KDDATEKDLS 529 DLVSEMEMMK539 MIGKHKNIIN549 LLGACTQDGP559 LYVIVEYASK569 GNLREYLRAR 579 RPPGMESYQM598 TFKDLVSCTY608 QLARGMEYLA618 SQKCIHRDLA628 ARNVLVTENN 638 VMKIADFGLA648 RDINNIDKKT660 TNGRLPVKWM670 APEALFDRVY680 THQSDVWSFG 690 VLMWEIFTLG700 GSPYPGIPVE710 ELFKLLKEGH720 RMDKPANCTN730 ELYMMMRDCW 740 HAVPSQRPTF750 KQLVEDLDRI760 LTLTT
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ARG573
4.967
ARG577
2.698
ARG580
3.731
MET584
3.420
GLU585
1.330
SER587
1.328
TYR588
4.811
ILE623
3.797
ARG625
3.342
ARG649
2.901
ILE651
3.805
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: AMP-PNP | Ligand Info | |||||
| Structure Description | Crystal Structure of FGF Receptor 2 Tyrosine Kinase Domain Harboring the D650V Activating Mutation | PDB:5UGL | ||||
| Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | Yes | [2] |
| PDB Sequence |
ELPEDPKWEF
476 PRDKLTLGKP486 LGEGAFGQVV496 MAEAVGIDKD506 KPKEAVTVAV516 KMLKDDATEK 526 DLSDLVSEME536 MMKMIGKHKN546 IINLLGACTQ556 DGPLYVIVEY566 ASKGNLREYL 576 RARRPMTFKD602 LVSCTYQLAR612 GMEYLASQKC622 IHRDLAARNV632 LVTENNVMKI 642 ADFGLARVIG663 RLPVKWMAPE673 ALFDRVYTHQ683 SDVWSFGVLM693 WEIFTLGGSP 703 YPGIPVEELF713 KLLKEGHRMD723 KPANCTNELY733 MMMRDCWHAV743 PSQRPTFKQL 753 VEDLDRILTL763 T
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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 .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .B:487 or .B:488 or .B:489 or .B:490 or .B:493 or .B:495 or .B:515 or .B:517 or .B:548 or .B:564 or .B:565 or .B:566 or .B:567 or .B:568 or .B:570 or .B:571 or .B:626 or .B:630 or .B:631 or .B:633 or .B:644; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU487
3.696
GLY488
3.647
GLU489
4.412
GLY490
4.366
GLY493
4.797
VAL495
3.685
ALA515
3.358
LYS517
4.061
ILE548
4.204
VAL564
3.508
GLU565
2.764
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| Ligand Name: 4-[4-(1-Amino-1-methylethyl)phenyl]-5-chloro-N-[4-(2-morpholin-4-ylethyl)phenyl]pyrimidin-2-amine | Ligand Info | |||||
| Structure Description | FGFr2 kinase domain | PDB:1OEC | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [3] |
| PDB Sequence |
ELPEDPKWEF
476 PRDKLTLGKP486 LGEGCFGQVV496 MAEAVGIKPK509 EAVTVAVKML519 KDDATEKDLS 529 DLVSEMEMMK539 MIGKHKNIIN549 LLGACTQDGP559 LYVIVEYASK569 GNLREYLRAR 579 REQMTFKDLV604 SCTYQLARGM614 EYLASQKCIH624 RDLAARNVLV634 TENNVMKIAD 644 FGLARDINNI654 DYYKKTTNGR664 LPVKWMAPEA674 LFDRVYTHQS684 DVWSFGVLMW 694 EIFTLGGSPY704 PGIPVEELFK714 LLKEGHRMDK724 PANCTNELYM734 MMRDCWHAVP 744 SQRPTFKQLV754 EDLDRILTLT764 T
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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 .AA2 or .AA22 or .AA23 or :3AA2;style chemicals stick;color identity;select .A:485 or .A:487 or .A:488 or .A:489 or .A:490 or .A:491 or .A:495 or .A:515 or .A:517 or .A:548 or .A:564 or .A:565 or .A:566 or .A:567 or .A:568 or .A:569 or .A:570 or .A:571 or .A:574 or .A:631 or .A:633 or .A:644; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LYS485
3.942
LEU487
3.690
GLY488
4.538
GLU489
3.441
GLY490
3.460
CYS491
4.767
VAL495
3.994
ALA515
3.537
LYS517
4.329
ILE548
4.231
VAL564
3.697
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| Ligand Name: (6s)-6-Phenyl-5,6-Dihydrobenzo[h]quinazolin-2-Amine | Ligand Info | |||||
| Structure Description | Crystal structure of the catalytic domain of FGFR2 kinase in complex with ARQ 069 | PDB:3RI1 | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [4] |
| PDB Sequence |
LPEDPKWEFP
477 RDKLTLGKPL487 GEGCFGQVVM497 AEAVGIDKDK507 PKEAVTVAVK517 MLKDDATEKD 527 LSDLVSEMEM537 MKMIGKHKNI547 INLLGACTQD557 GPLYVIVEYA567 SKGNLREYLR 577 ARRPPEQMTF600 KDLVSCTYQL610 ARGMEYLASQ620 KCIHRDLAAR630 NVLVTENNVM 640 KIADFGLARD650 INNIDYYKKT660 TNGRLPVKWM670 APEALFDRVY680 THQSDVWSFG 690 VLMWEIFTLG700 GSPYPGIPVE710 ELFKLLKEGH720 RMDKPANCTN730 ELYMMMRDCW 740 HAVPSQRPTF750 KQLVEDLDRI760 LTLTT
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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 .3RH or .3RH2 or .3RH3 or :33RH;style chemicals stick;color identity;select .A:487 or .A:488 or .A:495 or .A:515 or .A:517 or .A:534 or .A:538 or .A:548 or .A:564 or .A:565 or .A:566 or .A:567 or .A:568 or .A:570 or .A:633 or .A:643 or .A:644 or .A:645; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-ethyl-2-[[4-[[4-(4-methylpiperazin-1-yl)-3-(2-morpholin-4-ylethoxy)phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of FGFR2 in complex with 1,3,5-triazine derivative | PDB:6LVK | ||||
| Method | X-ray diffraction | Resolution | 2.29 Å | Mutation | No | [5] |
| PDB Sequence |
LPEDPKWEFP
477 RDKLTLGKPL487 GEGCFGQVVM497 AEAVGIDKDK507 PKEAVTVAVK517 MLKDDATEKD 527 LSDLVSEMEM537 MKMIGKHKNI547 INLLGACTQD557 GPLVIVEYAS568 KGNLREYLRA 578 RRPPGEEQMT599 FKDLVSCTYQ609 LARGMEYLAS619 QKCIHRDLAA629 RNVLVTENNV 639 MKIADFGLAR649 DINNIDYYKK659 TTNGRLPVKW669 MAPEALFDRV679 YTHQSDVWSF 689 GVLMWEIFTL699 GGSPYPGIPV709 EELFKLLKEG719 HRMDKPANCT729 NELYMMMRDC 739 WHAVPSQRPT749 FKQLVEDLDR759 ILTLTTN
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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 .EVC or .EVC2 or .EVC3 or :3EVC;style chemicals stick;color identity;select .A:485 or .A:487 or .A:488 or .A:489 or .A:492 or .A:495 or .A:497 or .A:515 or .A:517 or .A:534 or .A:548 or .A:564 or .A:565 or .A:566 or .A:567 or .A:568 or .A:569 or .A:570 or .A:571 or .A:574 or .A:630 or .A:631 or .A:632 or .A:633 or .A:643 or .A:644; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LYS485
3.439
LEU487
3.627
GLY488
3.970
GLU489
4.981
PHE492
3.864
VAL495
3.691
MET497
3.800
ALA515
3.320
LYS517
2.698
GLU534
4.948
ILE548
4.730
VAL564
3.760
GLU565
3.292
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| Ligand Name: N-ethyl-2-[[4-[[3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of FGFR2 in complex with 1,3,5-triazine derivative | PDB:6LVL | ||||
| Method | X-ray diffraction | Resolution | 2.98 Å | Mutation | No | [5] |
| PDB Sequence |
LPEDPKWEFP
477 RDKLTLGKPL487 GEGCFGQVVM497 AEAVGIDKDK507 PKEAVTVAVK517 MLKDDATEKD 527 LSDLVSEMEM537 MKMIGKHKNI547 INLLGACTQD557 GPLYVIVEYA567 SKGNLREYLR 577 ARRPPGEEQM598 TFKDLVSCTY608 QLARGMEYLA618 SQKCIHRDLA628 ARNVLVTENN 638 VMKIADFGLA648 RDINNIDYYK658 KTTNGRLPVK668 WMAPEALFDR678 VYTHQSDVWS 688 FGVLMWEIFT698 LGGSPYPGIP708 VEELFKLLKE718 GHRMDKPANC728 TNELYMMMRD 738 CWHAVPSQRP748 TFKQLVEDLD758 RILTLTTN
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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 .EVL or .EVL2 or .EVL3 or :3EVL;style chemicals stick;color identity;select .A:487 or .A:488 or .A:489 or .A:492 or .A:495 or .A:515 or .A:517 or .A:534 or .A:548 or .A:564 or .A:565 or .A:566 or .A:567 or .A:568 or .A:569 or .A:570 or .A:571 or .A:630 or .A:631 or .A:632 or .A:633 or .A:643 or .A:644; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU487
3.695
GLY488
3.793
GLU489
4.780
PHE492
3.582
VAL495
3.701
ALA515
3.570
LYS517
2.730
GLU534
4.964
ILE548
4.591
VAL564
3.932
GLU565
3.394
TYR566
3.818
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| Ligand Name: 5'-O-[(S)-Hydroxy{[(S)-Hydroxy(Methyl)phosphoryl]oxy}phosphoryl]adenosine | Ligand Info | |||||
| Structure Description | Structure of phosphotransferase | PDB:3B2T | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [6] |
| PDB Sequence |
SEYELPEDPK
473 WEFPRDKLTL483 GKPLGEGCFG493 QVVMAEAVGI503 DPKEAVTVAV516 KMLKDDATEK 526 DLSDLVSEME536 MMKMIGKHKN546 IINLLGACTQ556 DGPLYVIVEY566 ASKGNLREYL 576 RARRPPQMTF600 KDLVSCTYQL610 ARGMEYLASQ620 KCIHRDLTAR630 NVLVTENNVM 640 KIADFGLARD650 INNIDYYKKT660 TNGRLPVKWM670 APEALFDRVY680 THQSDVWSFG 690 VLMWEIFTLG700 GSPYPGIPVE710 ELFKLLKEGH720 RMDKPANCTN730 ELYMMMRDCW 740 HAVPSQRPTF750 KQLVEDLDRI760 LTLTTNQE
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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 .M33 or .M332 or .M333 or :3M33;style chemicals stick;color identity;select .A:487 or .A:488 or .A:489 or .A:490 or .A:493 or .A:495 or .A:515 or .A:517 or .A:548 or .A:564 or .A:565 or .A:566 or .A:567 or .A:570 or .A:571 or .A:630 or .A:631 or .A:633 or .A:644; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1-[4-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]phenyl]piperidin-1-yl]prop-2-en-1-one | Ligand Info | |||||
| Structure Description | Crystal structure of FGFR2 kinase domain gatekeeper mutant V564F in complex with covalent compound 19 | PDB:7KIA | ||||
| Method | X-ray diffraction | Resolution | 2.22 Å | Mutation | Yes | [7] |
| PDB Sequence |
ELPEDPKWEF
476 PRDKLTLGKP486 LGEGCFGQVV496 MAEAVGIDKD506 KPKEAVTVAV516 KMLKDDATEK 526 DLSDLVSEME536 MMKMIGKHKN546 IINLLGACTQ556 DGPLYVIFEY566 ASKGNLREYL 576 RARRPPGEEQ597 MTFKDLVSCT607 YQLARGMEYL617 ASQKCIHRDL627 AARNVLVTEN 637 NVMKIADFGL647 ARDINNIDYY657 KKTTNGRLPV667 KWMAPEALFD677 RVYTHQSDVW 687 SFGVLMWEIF697 TLGGSPYPGI707 PVEELFKLLK717 EGHRMDKPAN727 CTNELYMMMR 737 DCWHAVPSQR747 PTFKQLVEDL757 DRILTLT
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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 .WFD or .WFD2 or .WFD3 or :3WFD;style chemicals stick;color identity;select .A:487 or .A:488 or .A:489 or .A:490 or .A:491 or .A:492 or .A:493 or .A:495 or .A:515 or .A:517 or .A:534 or .A:548 or .A:564 or .A:565 or .A:566 or .A:567 or .A:568 or .A:569 or .A:570 or .A:626 or .A:631 or .A:633 or .A:644; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU487
3.448
GLY488
3.787
GLU489
3.823
GLY490
3.429
CYS491
1.594
PHE492
3.684
GLY493
4.907
VAL495
3.632
ALA515
3.388
LYS517
3.034
GLU534
4.945
ILE548
4.103
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| Ligand Name: N-[4-[(E)-2-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]ethenyl]phenyl]prop-2-enamide | Ligand Info | |||||
| Structure Description | Crystal structure of FGFR2 kinase domain gatekeeper mutant V564F in complex with covalent compound 3 | PDB:7KIE | ||||
| Method | X-ray diffraction | Resolution | 2.47 Å | Mutation | Yes | [7] |
| PDB Sequence |
YELPEDPKWE
475 FPRDKLTLGK485 PLGEGCFGQV495 VMAEAVGIDK505 DKPKEAVTVA515 VKMLKDDATE 525 KDLSDLVSEM535 EMMKMIGKHK545 NIINLLGACT555 QDGPLYVIFE565 YASKGNLREY 575 LRARRPPGPE595 EQMTFKDLVS605 CTYQLARGME615 YLASQKCIHR625 DLAARNVLVT 635 ENNVMKIADF645 GLARDINNID655 YYKKTTNGRL665 PVKWMAPEAL675 FDRVYTHQSD 685 VWSFGVLMWE695 IFTLGGSPYP705 GIPVEELFKL715 LKEGHRMDKP725 ANCTNELYMM 735 MRDCWHAVPS745 QRPTFKQLVE755 DLDRILTLTT765 N
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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 .WF7 or .WF72 or .WF73 or :3WF7;style chemicals stick;color identity;select .A:487 or .A:488 or .A:489 or .A:490 or .A:491 or .A:492 or .A:493 or .A:495 or .A:515 or .A:548 or .A:564 or .A:565 or .A:566 or .A:567 or .A:568 or .A:569 or .A:570 or .A:571 or .A:633; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: ethyl [4-({3-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-5-yl}sulfonyl)-1H-imidazol-1-yl]acetate | Ligand Info | |||||
| Structure Description | The cocrystal structure of FGFR2 bound with compound 14 harboring 5H-pyrrolo[2,3-b]pyrazine scaffold | PDB:6AGX | ||||
| Method | X-ray diffraction | Resolution | 2.95 Å | Mutation | Yes | [8] |
| PDB Sequence |
ELPEDPKWEF
476 PRDKLTLGKP486 LGEGCFGQVV496 MAEAVGIDKD506 KPKEAVTVAV516 KMLKDDATEK 526 DLSDLVSEME536 MMKMIGKHKN546 IINLLGACTQ556 DGPLYVIVEY566 ASKGNLREYL 576 RARRPINRVP594 EEQMTFKDLV604 SCTYQLARGM614 EYLASQKCIH624 RDLTARNVLV 634 TENNVMKIAD644 FGLARDIKKT660 TNGRLPVKWM670 APEALFDRVY680 THQSDVWSFG 690 VLMWEIFTLG700 GSPYPGIPVE710 ELFKLLKEGH720 RMDKPANCTN730 ELYMMMRDCW 740 HAVPSQRPTF750 KQLVEDLDRI760 LTLT
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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 .9WX or .9WX2 or .9WX3 or :39WX;style chemicals stick;color identity;select .A:487 or .A:488 or .A:495 or .A:515 or .A:517 or .A:531 or .A:534 or .A:538 or .A:548 or .A:562 or .A:564 or .A:565 or .A:566 or .A:567 or .A:570 or .A:571 or .A:630 or .A:631 or .A:633 or .A:642 or .A:643 or .A:644 or .A:645; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU487
3.559
GLY488
3.448
VAL495
3.847
ALA515
3.759
LYS517
2.984
LEU531
4.397
GLU534
3.395
MET538
4.130
ILE548
3.371
VAL562
3.700
VAL564
3.758
GLU565
3.995
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases. Mol Cell. 2007 Sep 7;27(5):717-30. | ||||
| REF 2 | Elucidation of a four-site allosteric network in fibroblast growth factor receptor tyrosine kinases. Elife. 2017 Feb 6;6:e21137. | ||||
| REF 3 | The Crystal Structure of the Fgfr2 Tyrosine Kinase Domain in Complex with 4-Aryl-2-Phenylamino Pyrimidine Angiogenesis Inhibitors | ||||
| REF 4 | A novel mode of protein kinase inhibition exploiting hydrophobic motifs of autoinhibited kinases: discovery of ATP-independent inhibitors of fibroblast growth factor receptor. J Biol Chem. 2011 Jun 10;286(23):20677-87. | ||||
| REF 5 | Structure-based drug design of 1,3,5-triazine and pyrimidine derivatives as novel FGFR3 inhibitors with high selectivity over VEGFR2. Bioorg Med Chem. 2020 May 15;28(10):115453. | ||||
| REF 6 | Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19802-7. | ||||
| REF 7 | Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3. ACS Med Chem Lett. 2020 Dec 2;12(1):93-98. | ||||
| REF 8 | The cocrystal structure of FGFR2 bound with compound 14 harboring 5H-pyrrolo[2,3-b]pyrazine scaffold | ||||
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