Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T74977 | Target Info | |||
| Target Name | Dual specificity protein kinase TTK (MPS1) | ||||
| Synonyms | Tyrosine threonine kinase; Phosphotyrosine picked threonine-protein kinase; PYT; MPS1L1 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | TTK | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Phosphonothreonine | Ligand Info | |||
| Canonical SMILES | CC(C(C(=O)O)N)OP(=O)(O)O | ||||
| InChI | 1S/C4H10NO6P/c1-2(3(5)4(6)7)11-12(8,9)10/h2-3H,5H2,1H3,(H,6,7)(H2,8,9,10)/t2-,3+/m1/s1 | ||||
| InChIKey | USRGIUJOYOXOQJ-GBXIJSLDSA-N | ||||
| PubChem Compound ID | 3246323 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5AP1 Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [1] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 VVKDVGVNYM690 PPEAIKDMSS700 KSKISPKSDV717 WSLGCILYYM727 TYGKTPFQQI 737 INQISKLHAI747 IDPNHEIEFP757 DIPEKDLQDV767 LKCCLKRDPK777 QRISIPELLA 787 HPYVQIQT
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| PDB ID: 5N93 TTK kinase domain in complex with TC-Mps1-12 | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPDV 684 GVNYMPPEAI695 KDMSKISPKS715 DVWSLGCILY725 YMTYGKTPFQ735 QIINQISKLH 745 AIIDPNHEIE755 FPDIPEKDLQ765 DVLKCCLKRD775 PKQRISIPEL785 LAHPYVQIQ |
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| PDB ID: 5AP0 Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [1] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQVGVN 688 YMPPEAIKDM698 ISPKSDVWSL720 GCILYYMTYG730 KTPFQQIINQ740 ISKLHAIIDP 750 NHEIEFPDIP760 EKDLQDVLKC770 CLKRDPKQRI780 SIPELLAHPY790 VQIQT |
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| PDB ID: 5N87 TTK kinase domain in complex with NTRC 0066-0 | ||||||
| Method | X-ray diffraction | Resolution | 2.29 Å | Mutation | No | [2] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQQVGVN 688 YMPPEAIKDM698 KISPKSDVWS719 LGCILYYMTY729 GKTPFQQIIN739 QISKLHAIID 749 PNHEIEFPDI759 PEKDLQDVLK769 CCLKRDPKQR779 ISIPELLAHP789 YVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:647 or .A:649 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5N9S TTK kinase domain in complex with BAY 1161909 | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [2] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPDS 682 QVGVNYMPPE693 AIKDKISPKS715 DVWSLGCILY725 YMTYGKTPFQ735 QIINQISKLH 745 AIIDPNHEIE755 FPDIPEKDLQ765 DVLKCCLKRD775 PKQRISIPEL785 LAHPYVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:647 or .A:649 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4C4F Structure-based design of orally bioavailable pyrrolopyridine inhibitors of the mitotic kinase MPS1 | ||||||
| Method | X-ray diffraction | Resolution | 2.36 Å | Mutation | No | [3] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQQVGV 687 NYMPPEAIKD697 ISPKSDVWSL720 GCILYYMTYG730 KTPFQQIINQ740 ISKLHAIIDP 750 NHEIEFPDIP760 EKDLQDVLKC770 CLKRDPKQRI780 SIPELLAHPY790 VQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:647 or .A:649 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4C4J Structure-based design of orally bioavailable pyrrolopyridine inhibitors of the mitotic kinase MPS1 | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [3] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPDT 675 VGVNYMPPEA694 IKDMSSKISP713 KSDVWSLGCI723 LYYMTYGKTP733 FQQIINQISK 743 LHAIIDPNHE753 IEFPDIPEKD763 LQDVLKCCLK773 RDPKQRISIP783 ELLAHPYVQI 793 Q
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:614 or .A:649 or .A:650 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732 or .A:735; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4CV9 MPS1 kinase with 3-aminopyridin-2-one inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [4] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANVGVNY 689 MPPEAIKDMS699 ISPKSDVWSL720 GCILYYMTYG730 KTPFQQIINQ740 ISKLHAIIDP 750 NHEIEFPDIP760 EKDLQDVLKC770 CLKRDPKQRI780 SIPELLAHPY790 VQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:649 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4CVA MPS1 kinase with 3-aminopyridin-2-one inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [5] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANVGVNY 689 MPPEAIKDMK710 ISPKSDVWSL720 GCILYYMTYG730 KTPFQQIINQ740 ISKLHAIIDP 750 NHEIEFPDIP760 EKDLQDVLKC770 CLKRDPKQRI780 SIPELLAHPY790 VQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:649 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732 or .A:735; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5N7V TTK kinase domain in complex with MPI-0479605 | ||||||
| Method | X-ray diffraction | Resolution | 2.52 Å | Mutation | No | [2] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPDS 682 QVGVNYMPPE693 AIKDMKISPK714 SDVWSLGCIL724 YYMTYGKTPF734 QQIINQISKL 744 HAIIDPNHEI754 EFPDIPEKDL764 QDVLKCCLKR774 DPKQRISIPE784 LLAHPYVQIQ 794
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:649 or .A:682 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:740; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3H9F Crystal Structure of Human Dual Specificity Protein Kinase (TTK) in complex with a pyrimido-diazepin ligand | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [6] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 GTVNYMPPEA694 IKDMSKISPK714 SDVWSLGCIL724 YYMTYGKTPF734 QQIINQISKL 744 HAIIDPNHEI754 EFPDIPEKDL764 QDVLKCCLKR774 DPKQRISIPE784 LLAHPYVQIQ 794
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:673 or .A:674; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4C4E Structure-based design of orally bioavailable pyrrolopyridine inhibitors of the mitotic kinase MPS1 | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [3] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPQV 684 GVNYMPPEAI695 KDISPKSDVW718 SLGCILYYMT728 YGKTPFQQII738 NQISKLHAII 748 DPNHEIEFPD758 IPEKDLQDVL768 KCCLKRDPKQ778 RISIPELLAH788 PYVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:647 or .A:649 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690 or .A:732; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4C4G Structure-based design of orally bioavailable pyrrolopyridine inhibitors of the mitotic kinase MPS1 | ||||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [3] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIAVGVNYM 690 PPEAIKDISP713 KSDVWSLGCI723 LYYMTYGKTP733 FQQIINQISK743 LHAIIDPNHE 753 IEFPDIPEKD763 LQDVLKCCLK773 RDPKQRISIP783 ELLAHPYVQI793 Q |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:649 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732 or .A:740; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5AP3 Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. | ||||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | Yes | [1] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNGWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANSQVGVN 688 YMPPEAIKDI711 SPKSDVWSLG721 CILYYMTYGK731 TPFQQIINQI741 SKLHAIIDPN 751 HEIEFPDIPE761 KDLQDVLKCC771 LKRDPKQRIS781 IPELLAHPYV791 QIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:647 or .A:649 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5NAD TTK kinase domain in complex with BAY 1217389 | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [2] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPDV 687 NYMPPEAIKD697 MKISPKSDVW718 SLGCILYYMT728 YGKTPFQQII738 NQISKLHAII 748 DPNHEIEFPD758 IPEKDLQDVL768 KCCLKRDPKQ778 RISIPELLAH788 PYVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:649 or .A:687 or .A:688 or .A:689 or .A:732 or .A:735; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5AP4 Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. | ||||||
| Method | X-ray diffraction | Resolution | 2.85 Å | Mutation | Yes | [1] |
| PDB Sequence |
FQSMSVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNGWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANMQPDQ 683 VGVNYMPPEA694 IKDISPKSDV717 WSLGCILYYM727 TYGKTPFQQI737 INQISKLHAI 747 IDPNHEIEFP757 DIPEKDLQDV767 LKCCLKRDPK777 QRISIPELLA787 HPYVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:647 or .A:649 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5NA0 TTK kinase domain in complex with a PEG-linked pyrimido-indolizine | ||||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [2] |
| PDB Sequence |
QSMSVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMVGVN 688 YMPPEAIKDI711 SPKSDVWSLG721 CILYYMTYGK731 TPFQQIINQI741 SKLHAIIDPN 751 HEIEFPDIPE761 KDLQDVLKCC771 LKRDPKQRIS781 IPELLAHPYV791 QIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:649 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6TNC X-RAY STRUCTURE OF MPS1 IN COMPLEX WITH COMPOUND 46 | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [7] |
| PDB Sequence |
ECISVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPVG 685 VNYMPPEAIK696 DMSKISPKSD716 VWSLGCILYY726 MTYGKTPFQQ736 IINQISKLHA 746 IIDPNHEIEF756 PDIPEKDLQD766 VLKCCLKRDP776 KQRISIPELL786 AHPYVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:649 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732 or .A:740; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6TNB X-RAY STRUCTURE OF MPS1 IN COMPLEX WITH COMPOUND 41 | ||||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [7] |
| PDB Sequence |
CISVKGRIYS
526 ILKQIGSGGS536 SKVFQVLNEK546 KQIYAIKYVN556 LEEADNQTLD566 SYRNEIAYLN 576 KLQQHSDKII586 RLYDYEITDQ596 YIYMVMECGN606 IDLNSWLKKK616 KSIDPWERKS 626 YWKNMLEAVH636 TIHQHGIVHS646 DLKPANFLIV656 DGMLKLIDFG666 IANGVNYMPP 692 EAIKDMKISP713 KSDVWSLGCI723 LYYMTYGKTP733 FQQIINQISK743 LHAIIDPNHE 753 IEFPDIPEKD763 LQDVLKCCLK773 RDPKQRISIP783 ELLAHPYVQI793 Q |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:649 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732 or .A:735; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5NTT Crystal structure of human Mps1 (TTK) C604Y mutant in complex with NMS-P715 | ||||||
| Method | X-ray diffraction | Resolution | 2.75 Å | Mutation | Yes | [8] |
| PDB Sequence |
ENLYFQSMSV
520 KGRIYSILKQ530 IGSGGSSKVF540 QVLNEKKQIY550 AIKYVNLEEA560 DNQTLDSYRN 570 EIAYLNKLQQ580 HSDKIIRLYD590 YEITDQYIYM600 VMEYGNIDLN610 SWLKKKKSID 620 PWERKSYWKN630 MLEAVHTIHQ640 HGIVHSDLKP650 ANFLIVDGML660 KLIDFGIANQ 670 MQPDTTSVVK680 DSQVGVNYMP691 PEAIKDMSKI711 SPKSDVWSLG721 CILYYMTYGK 731 TPFQQIINQI741 SKLHAIIDPN751 HEIEFPDIPE761 KDLQDVLKCC771 LKRDPKQRIS 781 IPELLAHPYV791 QIQTHP
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:649 or .A:682 or .A:683 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:690 or .A:732; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7CJA Crystal structure of TTK kinase domain in complex with compound 28 | ||||||
| Method | X-ray diffraction | Resolution | 2.49 Å | Mutation | No | [9] |
| PDB Sequence |
NECISVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 VGVNYMPPEA694 IKDMSSISPK714 SDVWSLGCIL724 YYMTYGKTPF734 QQIINQISKL 744 HAIIDPNHEI754 EFPDIPEKDL764 QDVLKCCLKR774 DPKQRISIPE784 LLAHPYVQIQ 794 TLE
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set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:614 or .A:673 or .A:674 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7CLH Crystal structure of TTK kinase domain in complex with compound 19 | ||||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [9] |
| PDB Sequence |
ECISVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPDV 684 GVNYMPPEAI695 KDMSISPKSD716 VWSLGCILYY726 MTYGKTPFQQ736 IINQISKLHA 746 IIDPNHEIEF756 PDIPEKDLQD766 VLKCCLKRDP776 KQRISIPELL786 AHPYVQIQT |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:649 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7CHN Crystal structure of TTK kinase domain in complex with compound 9 | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [9] |
| PDB Sequence |
NECISVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKIDPWERKS 626 YWKNMLEAVH636 TIHQHGIVHS646 DLKPANFLIV656 DGMLKLIDFG666 IANQMQPDVV 679 VGVNYMPPEA694 IKDMSKISPK714 SDVWSLGCIL724 YYMTYGKTPF734 QQIINQISKL 744 HAIIDPNHEI754 EFPDIPEKDL764 QDVLKCCLKR774 DPKQRISIPE784 LLAHPYVQIQ 794 TL
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:649 or .A:673 or .A:674 or .A:678 or .A:679 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732 or .A:735; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7CHT Crystal structure of TTK kinase domain in complex with compound 30 | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [9] |
| PDB Sequence |
NECISVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 VVNYMPPEAI695 KDMISPKSDV717 WSLGCILYYM727 TYGKTPFQQI737 INQISKLHAI 747 IDPNHEIEFP757 DIPEKDLQDV767 LKCCLKRDPK777 QRISIPELLA787 HPYVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:673 or .A:674 or .A:678 or .A:687 or .A:688 or .A:689 or .A:732 or .A:735 or .A:740 or .A:743; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4JS8 Crystal structure of TTK kinase domain with an inhibitor: 401348 | ||||||
| Method | X-ray diffraction | Resolution | 1.94 Å | Mutation | No | [10] |
| PDB Sequence |
NECISVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 VGVNYMPPEA694 IKDMSKISPK714 SDVWSLGCIL724 YYMTYGKTPF734 QQIINQISKL 744 HAIIDPNHEI754 EFPDIPEKDL764 QDVLKCCLKR774 DPKQRISIPE784 LLAHPYVQI |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:529 or .A:530 or .A:610 or .A:673 or .A:674 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7CIL Crystal structure of TTK kinase domain in complex with compound 7 | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [9] |
| PDB Sequence |
NECISVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 VGVNYMPPEA694 IKDMSSKSKI711 SPKSDVWSLG721 CILYYMTYGK731 TPFQQIINQI 741 SKLHAIIDPN751 HEIEFPDIPE761 KDLQDVLKCC771 LKRDPKQRIS781 IPELLAHPYV 791 QIQT
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:649 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:732 or .A:735; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4O6L Crystal Structure of TTK kinase domain with an inhibitor: 401498 (N-[(1R)-1-(2-chlorophenyl)propyl]-3-{4-[(1-methylpiperidin-4-yl)oxy]phenyl}-1H-indazole-5-carboxamide) | ||||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | No | [11] |
| PDB Sequence |
NECISVKGRI
524 YSILKQIGSG534 GSSKVFQVLN544 EKKQIYAIKY554 VNLEEADNQT564 LDSYRNEIAY 574 LNKLQQHSDK584 IIRLYDYEIT594 DQYIYMVMEC604 GNIDLNSWLK614 KKKSIDPWER 624 KSYWKNMLEA634 VHTIHQHGIV644 HSDLKPANFL654 IVDGMLKLID664 FGIANQMQPD 674 TVNYMPPEAI695 KDMSISPKSD716 VWSLGCILYY726 MTYGKTPFQQ736 IINQISKLHA 746 IIDPNHEIEF756 PDIPEKDLQD766 VLKCCLKRDP776 KQRISIPELL786 AHPYVQI |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:529 or .A:530 or .A:673 or .A:674; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7CHM Crystal structure of TTK kinase domain in complex with compound 8 | ||||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [9] |
| PDB Sequence |
ECISVKGRIY
525 SILKQIGSGG535 SSKVFQVLNE545 KKQIYAIKYV555 NLEEADNQTL565 DSYRNEIAYL 575 NKLQQHSDKI585 IRLYDYEITD595 QYIYMVMECG605 NIDLNSWLKK615 KKSIDPWERK 625 SYWKNMLEAV635 HTIHQHGIVH645 SDLKPANFLI655 VDGMLKLIDF665 GIANQMQPDV 684 GVNYMPPEAI695 KDMSISPKSD716 VWSLGCILYY726 MTYGKTPFQQ736 IINQISKLHA 746 IIDPNHEIEF756 PDIPEKDLQD766 VLKCCLKRDP776 KQRISIPELL786 AHPYVQIQ |
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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 .TPO or .TPO2 or .TPO3 or :3TPO;style chemicals stick;color identity;select .A:610 or .A:673 or .A:674 or .A:684 or .A:685 or .A:687 or .A:688 or .A:689 or .A:735; 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 | Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. Cancer Res. 2015 Aug 15;75(16):3340-54. | ||||
| REF 2 | Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity. J Mol Biol. 2017 Jul 7;429(14):2211-2230. | ||||
| REF 3 | Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1). J Med Chem. 2013 Dec 27;56(24):10045-65. | ||||
| REF 4 | Protein Kinase Selectivity of a 3-Aminopyridin-2- One Based Fragment Library, Identification of 3-Amino-5-(Pyridin-4-Yl)Pyridin-2(1H)-One as a Novel Scaffold for Mps1 Inhibition | ||||
| REF 5 | Protein Kinase Selectivity of a 3-Aminopyridin-2- One Based Fragment Library, Identification of 3-Amino-5-(Pyridin-4-Yl)Pyridin-2(1H)-One as a Novel Scaffold for Mps1 Inhibition | ||||
| REF 6 | Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol. 2010 May;6(5):359-68. | ||||
| REF 7 | Treating Cancer by Spindle Assembly Checkpoint Abrogation: Discovery of Two Clinical Candidates, BAY 1161909 and BAY 1217389, Targeting MPS1 Kinase. J Med Chem. 2020 Aug 13;63(15):8025-8042. | ||||
| REF 8 | Understanding inhibitor resistance in Mps1 kinase through novel biophysical assays and structures. J Biol Chem. 2017 Sep 1;292(35):14496-14504. | ||||
| REF 9 | X-ray Crystal Structure-Guided Design and Optimization of 7H-Pyrrolo[2,3-d]pyrimidine-5-carbonitrile Scaffold as a Potent and Orally Active Monopolar Spindle 1 Inhibitor. J Med Chem. 2021 May 27;64(10):6985-6995. | ||||
| REF 10 | Crystal structure of TTK kinase domain with an inhibitor: 401348 | ||||
| REF 11 | Crystal Structure of TTK kinase domain with an inhibitor: 401498 | ||||
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