Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T20973 | Target Info | |||
| Target Name | Cyclin-dependent kinase 5 (CDK5) | ||||
| Synonyms | Tau protein kinase II catalytic subunit; TPKII catalytic subunit; Serine/threonine-protein kinase PSSALRE; Serine/threonine protein kinase PSSALRE; Proline-directed protein kinase F(A) (PDPK F(A)); Proline-directed protein kinase 33 kDa subunit; PDPK; Cyclin-dependent-like kinase 5; Cyclin-dependent kinase 5 (CDK5); Cell division protein kinase 5; CDKN5 | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | CDK5 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: R-roscovitine | Ligand Info | |||||
| Structure Description | Structural mechanism for the inhibition of CD5-p25 from the roscovitine, aloisine and indirubin. | PDB:1UNL | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [1] |
| PDB Sequence |
MQKYEKLEKI
10 GEGTYGTVFK20 AKNRETHEIV30 ALKRVRLDDD40 DEGVPSSALR50 EICLLKELKH 60 KNIVRLHDVL70 HSDKKLTLVF80 EFCDQDLKKY90 FDSCNGDLDP100 EIVKSFLFQL 110 LKGLGFCHSR120 NVLHRDLKPQ130 NLLINRNGEL140 KLANFGLARA150 FGIPVRCYSA 160 EVVTLWYRPP170 DVLFGAKLYS180 TSIDMWSAGC190 IFAELANAGR200 PLFPGNDVDD 210 QLKRIFRLLG220 TPTEEQWPSM230 TKLPDYKPYP240 MYPATTSLVN250 VVPKLNATGR 260 DLLQNLLKCN270 PVQRISAEEA280 LQHPYFSDFC290 PP
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| Ligand Name: Aloisine A | Ligand Info | |||||
| Structure Description | Structural mechanism for the inhibition of CDK5-p25 by roscovitine, aloisine and indirubin. | PDB:1UNG | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [1] |
| PDB Sequence |
MQKYEKLEKI
10 YGTVFKAKNR24 ETHEIVALKR34 VRLDDDDEGV44 PSSALREICL54 LKELKHKNIV 64 RLHDVLHSDK74 KLTLVFEFCD84 QDLKKYFDSC94 NGDLDPEIVK104 SFLFQLLKGL 114 GFCHSRNVLH124 RDLKPQNLLI134 NRNGELKLAN144 FGLARAFGIP154 VRCYSAEVVT 164 LWYRPPDVLF174 GAKLYSTSID184 MWSAGCIFAE194 LANAGRPLFP204 GNDVDDQLKR 214 IFRLLGTPTE224 EQWPSMTKLP234 DYKPYPMYPA244 TTSLVNVVPK254 LNATGRDLLQ 264 NLLKCNPVQR274 ISAEEALQHP284 YFSDFCPP
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| Ligand Name: Indirubin-3'-monoxime | Ligand Info | |||||
| Structure Description | Structural mechanism for the inhibition of CDK5-p25 by roscovitine, aloisine and indirubin. | PDB:1UNH | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | Yes | [1] |
| PDB Sequence |
QKYEKLEKIY
15 GTVFKAKNRH27 EIVALKRVRL37 DGVPSSALRE51 ICLLKELKHK61 NIVRLHDVLH 71 SDKKLTLVFE81 FCDQDLKKYF91 DSCNGDLDPE101 IVKSFLFQLL111 KGLGFCHSRN 121 VLHRDLKPQN131 LLINRNGELK141 LANFGLARAF151 GIPVRCYSAE161 VVTLWYRPPD 171 VLFGAKLYST181 SIDMWSAGCI191 FAELANAGRP201 LFPGNDVDDQ211 LKRIFRLLGT 221 PTEEQWPSMT231 KLPDYKPYPM241 YPATTSLVNV251 VPKLNATGRD261 LLQNLLKCNP 271 VQRISAEEAL281 QHPYFSD
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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 .IXM or .IXM2 or .IXM3 or :3IXM;style chemicals stick;color identity;select .A:10 or .A:18 or .A:31 or .A:33 or .A:64 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:89 or .A:130 or .A:133 or .A:143 or .A:144; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: [1-[3-Fluoranyl-4-[(2-piperidin-4-yloxy-1,6-naphthyridin-7-yl)amino]phenyl]pyrazol-3-yl]methanol | Ligand Info | |||||
| Structure Description | The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 1 | PDB:7VDP | ||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | No | [2] |
| PDB Sequence |
QKYEKLEKIG
11 EGTVFKAKNR24 ETHEIVALKR34 VRLDDDDEGV44 PSSALREICL54 LKELKHKNIV 64 RLHDVLHSDK74 KLTLVFEFCD84 QDLKKYFDSC94 NGDLDPEIVK104 SFLFQLLKGL 114 GFCHSRNVLH124 RDLKPQNLLI134 NRNGELKLAD144 FGLARAFGIP154 VRCYSAEVVT 164 LWYRPPDVLF174 GAKLYSTSID184 MWSAGCIFAE194 LANAGRPLFP204 GNDVDDQLKR 214 IFRLLGTPTE224 EQWPSMTKLP234 DYKPYPMYPA244 TTSLVNVVPK254 LNATGRDLLQ 264 NLLKCNPVQR274 ISAEEALQHP284 YFSDFCP
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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 .65L or .65L2 or .65L3 or :365L;style chemicals stick;color identity;select .A:10 or .A:12 or .A:18 or .A:31 or .A:33 or .A:64 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:89 or .A:130 or .A:131 or .A:133 or .A:143 or .A:144; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (1R)-1-[7-[(2-fluoranyl-4-pyrazol-1-yl-phenyl)amino]-1,6-naphthyridin-2-yl]-1-(1-methylpiperidin-4-yl)ethanol | Ligand Info | |||||
| Structure Description | The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 13 | PDB:7VDR | ||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [2] |
| PDB Sequence |
QKYEKLEKIG
11 EGTYGTVFKA21 KNRETHEIVA31 LKRVRLDDDD41 EGVPSSALRE51 ICLLKELKHK 61 NIVRLHDVLH71 SDKKLTLVFE81 FCDQDLKKYF91 DSCNGDLDPE101 IVKSFLFQLL 111 KGLGFCHSRN121 VLHRDLKPQN131 LLINRNGELK141 LADFGLARAF151 GIPVRCYSAE 161 VVTLWYRPPD171 VLFGAKLYST181 SIDMWSAGCI191 FAELANAGRP201 LFPGNDVDDQ 211 LKRIFRLLGT221 PTEEQWPSMT231 KLPDYKPYPM241 YPATTSLVNV251 VPKLNATGRD 261 LLQNLLKCNP271 VQRISAEEAL281 QHPYFSDFCP291
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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 .63I or .63I2 or .63I3 or :363I;style chemicals stick;color identity;select .A:10 or .A:15 or .A:18 or .A:31 or .A:33 or .A:51 or .A:64 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:89 or .A:130 or .A:131 or .A:133 or .A:143 or .A:144; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2-[[7-[[2-Fluoranyl-4-[3-(hydroxymethyl)pyrazol-1-yl]phenyl]amino]-1,6-naphthyridin-2-yl]-(1-methylpiperidin-4-yl)amino]ethanoic acid | Ligand Info | |||||
| Structure Description | The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 7 | PDB:7VDQ | ||||
| Method | X-ray diffraction | Resolution | 2.91 Å | Mutation | No | [2] |
| PDB Sequence |
QKYEKLEKIG
11 EGTYGTVFKA21 KNRETHEIVA31 LKRVRLDDDD41 EGVPSSALRE51 ICLLKELKHK 61 NIVRLHDVLH71 SDKKLTLVFE81 FCDQDLKKYF91 DSCNGDLDPE101 IVKSFLFQLL 111 KGLGFCHSRN121 VLHRDLKPQN131 LLINRNGELK141 LADFGLARAF151 GIPVRCYSAE 161 VVTLWYRPPD171 VLFGAKLYST181 SIDMWSAGCI191 FAELANAGRP201 LFPGNDVDDQ 211 LKRIFRLLGT221 PTEEQWPSMT231 KLPDYKPYPM241 YPATTSLVNV251 VPKLNATGRD 261 LLQNLLKCNP271 VQRISAEEAL281 QHPYFSDFCP291
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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 .64V or .64V2 or .64V3 or :364V;style chemicals stick;color identity;select .A:10 or .A:15 or .A:18 or .A:31 or .A:33 or .A:51 or .A:64 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:89 or .A:130 or .A:131 or .A:133 or .A:143 or .A:144 or .A:145; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-fluoranyl-4-[[2-[(1R)-1-(1-methylpiperidin-4-yl)-1-oxidanyl-ethyl]-1,6-naphthyridin-7-yl]amino]-2-morpholin-4-yl-benzenecarbonitrile | Ligand Info | |||||
| Structure Description | The structure of cyclin-dependent kinase 5 (CDK5) in complex with p25 and Compound 24 | PDB:7VDS | ||||
| Method | X-ray diffraction | Resolution | 3.05 Å | Mutation | No | [2] |
| PDB Sequence |
QKYEKLEKIG
11 EGTYGTVFKA21 KNRETHEIVA31 LKRVRLDDDD41 EGVPSSALRE51 ICLLKELKHK 61 NIVRLHDVLH71 SDKKLTLVFE81 FCDQDLKKYF91 DSCNGDLDPE101 IVKSFLFQLL 111 KGLGFCHSRN121 VLHRDLKPQN131 LLINRNGELK141 LADFGLARAF151 GIPVRCYSAE 161 VVTLWYRPPD171 VLFGAKLYST181 SIDMWSAGCI191 FAELANAGRP201 LFPGNDVDDQ 211 LKRIFRLLGT221 PTEEQWPSMT231 KLPDYKPYPM241 YPATTSLVNV251 VPKLNATGRD 261 LLQNLLKCNP271 VQRISAEEAL281 QHPYFSDFCP291
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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 .61U or .61U2 or .61U3 or :361U;style chemicals stick;color identity;select .A:8 or .A:9 or .A:10 or .A:18 or .A:31 or .A:33 or .A:51 or .A:64 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:89 or .A:128 or .A:130 or .A:131 or .A:133 or .A:143 or .A:144; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLU8
3.434
LYS9
4.755
ILE10
3.396
VAL18
3.809
ALA31
3.701
LYS33
3.692
GLU51
3.859
VAL64
3.608
PHE80
3.665
GLU81
3.444
PHE82
3.989
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| Ligand Name: 4-(1,3-Benzothiazol-2-Yl)thiophene-2-Sulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of compound 4a in complex with cdk5, showing an unusual binding mode to the hinge region via a water molecule | PDB:4AU8 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
GSQKYEKLEK
9 IGEGTYGTVF19 KAKNRETHEI29 VALKRVPSSA48 LREICLLKEL58 KHKNIVRLHD 68 VLHKLTLVFE81 FCDQDLKKYF91 DSCNGDLDPE101 IVKSFLFQLL111 KGLGFCHSRN 121 VLHRDLKPQN131 LLINRNGELK141 LADFGLARAF151 GIPVRSAEVV163 TLWYRPPDVL 173 FGAKLYSTSI183 DMWSAGCIFA193 ELANAGRPLF203 PGNDVDDQLK213 RIFRLLGTPT 223 EEQWPSMTKL233 PDYKPYPMYP243 ATTSLVNVVP253 KLNATGRDLL263 QNLLKCNPVQ 273 RISAEEALQH283 PYFSDF
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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 .Z3R or .Z3R2 or .Z3R3 or :3Z3R;style chemicals stick;color identity;select .A:10 or .A:11 or .A:18 or .A:31 or .A:33 or .A:64 or .A:80 or .A:81 or .A:82 or .A:83 or .A:84 or .A:85 or .A:86 or .A:89 or .A:130 or .A:133 or .A:143 or .A:144; 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 | Mechanism of CDK5/p25 binding by CDK inhibitors. J Med Chem. 2005 Feb 10;48(3):671-9. | ||||
| REF 2 | Discovery and Optimization of Highly Selective Inhibitors of CDK5. J Med Chem. 2022 Feb 24;65(4):3575-3596. | ||||
| REF 3 | Synthesis and structure-activity relationship of 4-(1,3-benzothiazol-2-yl)-thiophene-2-sulfonamides as cyclin-dependent kinase 5 (cdk5)/p25 inhibitors. Bioorg Med Chem Lett. 2012 Sep 15;22(18):5919-23. | ||||
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