Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T07173 | Target Info | |||
| Target Name | Tropomyosin-related kinase A (TrkA) | ||||
| Synonyms | gp140trk; Tyrosine kinase receptor A; Tyrosine kinase receptor; Trk-A; TRKA; TRK1-transforming tyrosine kinase protein; TRK1 transforming tyrosinekinase protein; TRK; P140-TrkA; Neurotrophic tyrosine kinase receptor type 1; NGF-trk receptor type A; MTC; High affinity nerve growth factor receptor | ||||
| Target Type | Successful Target | ||||
| Gene Name | NTRK1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | L-serine-O-phosphate | Ligand Info | |||
| Canonical SMILES | C(C(C(=O)O)N)OP(=O)(O)O | ||||
| InChI | 1S/C3H8NO6P/c4-2(3(5)6)1-10-11(7,8)9/h2H,1,4H2,(H,5,6)(H2,7,8,9)/t2-/m0/s1 | ||||
| InChIKey | BZQFBWGGLXLEPQ-REOHCLBHSA-N | ||||
| PubChem Compound ID | 68841 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6PL1 TRK-A IN COMPLEX WITH LIGAND 1B | ||||||
| Method | X-ray diffraction | Resolution | 2.03 Å | Mutation | No | [1] |
| PDB Sequence |
ACVHHIKRRD
509 IVLKWELGEG519 AFGKVFLAEC529 HNLLPEQDKM539 LVAVKALKES552 ARQDFQREAE 562 LLTMLQHQHI572 VRFFGVCTEG582 RPLLMVFEYM592 RHGDLNRFLR602 SHGPDAKLLA 612 GGEDVAPGPL622 GLGQLLAVAS632 QVAAGMVYLA642 GLHFVHRDLA652 TRNCLVGQGL 662 VVKIGDFGMS672 RDIYTDYYRV683 TMLPIRWMPP696 ESILYRKFTT706 ESDVWSFGVV 716 LWEIFTYGKQ726 PWYQLSNTEA736 IDCITQGREL746 ERPRACPPEV756 YAIMRGCWQR 766 EPQQRHSIKD776 VHARLQALAQ786 APPVYLDVL
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| PDB ID: 6PL4 TRK-A IN COMPLEX WITH LIGAND 1 | ||||||
| Method | X-ray diffraction | Resolution | 2.06 Å | Mutation | No | [2] |
| PDB Sequence |
GLQGHIACVH
503 HIKRRDIVLK513 WELGEGAFGK523 VFLAECHNLL533 PEQDKMLVAV543 KALKEASESA 553 RQDFQREAEL563 LTMLQHQHIV573 RFFGVCTEGR583 PLLMVFEYMR593 HGDLNRFLRS 603 HGPDAAGGED616 VAPGPLGLGQ626 LLAVASQVAA636 GMVYLAGLHF646 VHRDLATRNC 656 LVGQGLVVKI666 GDFGMSRDIY676 TDYYRVGGRT687 MLPIRWMPPE697 SILYRKFTTE 707 SDVWSFGVVL717 WEIFTYGKQP727 WYQLSNTEAI737 DCITQGRELE747 RPRACPPEVY 757 AIMRGCWQRE767 PQQRHSIKDV777 HARLQALAQA787 PPVYLDVL
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| PDB ID: 6PMC TRK-A IN COMPLEX WITH LIGAND 1a | ||||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [3] |
| PDB Sequence |
ACVHHIKRRD
509 IVLKWELGEG519 AFGKVFLAEC529 HNLLPEQDKM539 LVAVKALKEA549 SESARQDFQR 559 EAELLTMLQH569 QHIVRFFGVC579 TEGRPLLMVF589 EYMRHGDLNR599 FLRSHGGGED 616 VAPGPLGLGQ626 LLAVASQVAA636 GMVYLAGLHF646 VHRDLATRNC656 LVGQGLVVKI 666 GDFGMSRDIY676 TDYYRVGGRT687 MLPIRWMPPE697 SILYRKFTTE707 SDVWSFGVVL 717 WEIFTYGKQP727 WYQLSNTEAI737 DCITQGRELE747 RPRACPPEVY757 AIMRGCWQRE 767 PQQRHSIKDV777 HARLQALAQA787 PPVYLDVL
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| PDB ID: 6PMA TRK-A IN COMPLEX WITH LIGAND | ||||||
| Method | X-ray diffraction | Resolution | 2.53 Å | Mutation | No | [3] |
| PDB Sequence |
ACVHHIKRRD
509 IVLKWELGEG519 AFGKVFLAEC529 HNLLPEQDKM539 LVAVKALKES552 ARQDFQREAE 562 LLTMLQHQHI572 VRFFGVCTEG582 RPLLMVFEYM592 RHGDLNRFLR602 SHGPDAAGGE 615 DVAPGPLGLG625 QLLAVASQVA635 AGMVYLAGLH645 FVHRDLATRN655 CLVGQGLVVK 665 IGDFGMSRDI675 YTDYYRVGGR686 TMLPIRWMPP696 ESILYRKFTT706 ESDVWSFGVV 716 LWEIFTYGKQ726 PWYQLSNTEA736 IDCITQGREL746 ERPRACPPEV756 YAIMRGCWQR 766 EPQQRHSIKD776 VHARLQALAQ786 APPVYLDVL
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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 .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:678 or .A:679 or .A:680 or .A:688; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6PL2 TRK-A IN COMPLEX WITH LIGAND 1a | ||||||
| Method | X-ray diffraction | Resolution | 2.59 Å | Mutation | No | [4] |
| PDB Sequence |
DACVHHIKRR
508 DIVLKWELGE518 GAFGKVFLAE528 CHNLLPEQDK538 MLVAVKALKE548 ASESARQDFQ 558 REAELLTMLQ568 HQHIVRFFGV578 CTEGRPLLMV588 FEYMRHGDLN598 RFLRSHGPDA 608 KLLAGGEDVA618 PGPLGLGQLL628 AVASQVAAGM638 VYLAGLHFVH648 RDLATRNCLV 658 GQGLVVKIGD668 FGMSRDIYTD679 YYRVGGRTML689 PIRWMPPESI699 LYRKFTTESD 709 VWSFGVVLWE719 IFTYGKQPWY729 QLSNTEAIDC739 ITQGRELERP749 RACPPEVYAI 759 MRGCWQREPQ769 QRHSIKDVHA779 RLQALAQAPP789 VYLDVL
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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 .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:673 or .A:674 or .A:675 or .A:676 or .A:678 or .A:679 or .A:680 or .A:682 or .A:688; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6PME TRK-A IN COMPLEX WITH LIGAND | ||||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [3] |
| PDB Sequence |
ACVHHIKRRD
509 IVLKWELGEG519 AFGKVFLAEC529 HNKMLVAVKA545 LKEASESARQ555 DFQREAELLT 565 MLQHQHIVRF575 FGVCTEGRPL585 LMVFEYMRHG595 DLNRFLRSHG605 PDGPLGLGQL 627 LAVASQVAAG637 MVYLAGLHFV647 HRDLATRNCL657 VGQGLVVKIG667 DFGMSRDIYT 678 DYYRVTMLPI691 RWMPPESILY701 RKFTTESDVW711 SFGVVLWEIF721 TYGKQPWYQL 731 SNTEAIDCIT741 QGRELERPRA751 CPPEVYAIMR761 GCWQREPQQR771 HSIKDVHARL 781 QALAQAP
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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 .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:678 or .A:679 or .A:680 or .A:682 or .A:688; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6NPT TRK-A IN COMPLEX WITH LIGAND 1 | ||||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [5] |
| PDB Sequence |
IENCVHHIKR
507 RDIVLKWELG517 EGAFGKVFLA527 ECHNLLPEQD537 KMLVAVKALK547 EARQDFQREA 561 ELLTMLQHQH571 IVRFFGVCTE581 GRPLLMVFEY591 MRHGDLNRFL601 RSHGPGGEDV 617 APGPLGLGQL627 LAVASQVAAG637 MVYLAGLHFV647 HRDLATRNCL657 VGQGLVVKIG 667 DFGMSRDIYT678 DYYRVGGRTM688 LPIRWMPPES698 ILYRKFTTES708 DVWSFGVVLW 718 EIFTYGKQPW728 YQLSNTEAID738 CITQGRELER748 PRACPPEVYA758 IMRGCWQREP 768 QQRHSIKDVH778 ARLQALAQAP788 PVYLDVL
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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 .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:672 or .A:673 or .A:674 or .A:675 or .A:676 or .A:678 or .A:679 or .A:680 or .A:688; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5WR7 Crystal structure of Trk-A complexed with a selective inhibitor CH7057288 | ||||||
| Method | X-ray diffraction | Resolution | 2.76 Å | Mutation | No | [6] |
| PDB Sequence |
HIIENPQYFS
498 DACVHHIKRR508 DIVLKWELGE518 GAFGKVFLAE528 CHNLLPEQDK538 MLVAVKALKE 548 ASESARQDFQ558 REAELLTMLQ568 HQHIVRFFGV578 CTEGRPLLMV588 FEYMRHGDLN 598 RFLRSHGPDA608 KLLAGGEDVA618 PGPLGLGQLL628 AVASQVAAGM638 VYLAGLHFVH 648 RDLATRNCLV658 GQGLVVKIGD668 FGMSRDIYTD679 YYRVGTMLPI691 RWMPPESILY 701 RKFTTESDVW711 SFGVVLWEIF721 TYGKQPWYQL731 SNTEAIDCIT741 QGRELERPRA 751 CPPEVYAIMR761 GCWQREPQQR771 HSIKDVHARL781 QALAQAPPVY791 L |
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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 .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:673 or .A:674 or .A:675 or .A:676 or .A:678 or .A:679 or .A:680 or .A:688; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Lead identification and characterization of hTrkA type 2 inhibitors. Bioorg Med Chem Lett. 2019 Nov 15;29(22):126680. | ||||
| REF 2 | In Pursuit of an Allosteric Human Tropomyosin Kinase A (hTrkA) Inhibitor for Chronic Pain. doi:10.1021/acsmedchemlett.1c00483. | ||||
| REF 3 | Synthetic inhibitor leads of human tropomyosin receptor kinase A (hTrkA). RSC Med Chem. 2020 Jan 10;11(3):370-377. | ||||
| REF 4 | Type 2 inhibitor leads of human tropomyosin receptor kinase (hTrkA). Bioorg Med Chem Lett. 2019 Oct 1;29(19):126624. | ||||
| REF 5 | Deciphering the Allosteric Binding Mechanism of the Human Tropomyosin Receptor Kinase A ( hTrkA) Inhibitors. ACS Chem Biol. 2019 Jun 21;14(6):1205-1216. | ||||
| REF 6 | Selective TRK Inhibitor CH7057288 against TRK Fusion-Driven Cancer. Mol Cancer Ther. 2018 Dec;17(12):2519-2529. | ||||
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