Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T70851 | Target Info | |||
| Target Name | Extracellular signal-regulated kinase 5 (ERK5) | ||||
| Synonyms | PRKM7; Mitogen-activated protein kinase 7; MAPK 7; MAP kinase 7; ERK-5; Big MAP kinase 1; BMK1; BMK-1 | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | MAPK7 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: AMP-PNP | Ligand Info | |||||
| Structure Description | Crystal structure of the ERK5 kinase domain in complex with an MKK5 binding fragment | PDB:4IC7 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [1] |
| PDB Sequence |
DVTFDVGDEY
55 EIIETIGNGA65 YGVVSSARRR75 LTGQQVAIKK85 IPNAFDVVTN95 AKRTLRELKI 105 LKHFKHDNII115 AIKDILRPTV125 PYGEFKSVYV135 VLDLMESDLH145 QIIHSSQPLT 155 LEHVRYFLYQ165 LLRGLKYMHS175 AQVIHRDLKP185 SNLLVNENCE195 LKIGDFGMAR 205 GLCTSPAEHQ215 YFMTEYVATR225 WYRAPELMLS235 LHEYTQAIDL245 WSVGCIFGEM 255 LARRQLFPGK265 NYVHQLQLIM275 MVLGTPSPAV285 IQAVGAERVR295 AYIQSLPPRQ 305 PVPWETVYPG315 ADRQALSLLG325 RMLRFEPSAR335 ISAAAALRHP345 FLAKYHDPDD 355 EPDCAPPFDF365 AFDREALTRE375 RIKEAIVAEI385 EDFHARREGI395 RQQIR |
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ILE61
3.857
GLY62
3.211
ASN63
3.812
GLY64
3.882
ALA65
2.757
TYR66
3.521
GLY67
4.530
VAL69
3.452
ALA82
3.670
LYS84
2.706
ARG98
3.140
|
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| Ligand Name: XMD8-92 | Ligand Info | |||||
| Structure Description | ERK5 IN COMPLEX WITH SMALL MOLECULE | PDB:5BYY | ||||
| Method | X-ray diffraction | Resolution | 2.79 Å | Mutation | No | [2] |
| PDB Sequence |
FDVGDEYEII
58 ETIGNGAYGV68 VSSARRRLTG78 QQVAIKKIPN88 AFDVVTNAKR98 TLRELKILKH 108 FKHDNIIAIK118 DILRPTVPYG128 EFKSVYVVLD138 LMESDLHQII148 HSSQPLTLEH 158 VRYFLYQLLR168 GLKYMHSAQV178 IHRDLKPSNL188 LVNENCELKI198 GDFGMARGLY 216 FMTEYVATRW226 YRAPELMLSL236 HEYTQAIDLW246 SVGCIFGEML256 ARRQLFPGKN 266 YVHQLQLIMM276 VLGTPSPAVI286 QAVGAERVRA296 YIQSLPPRQP306 VPWETVYPGA 316 DRQALSLLGR326 MLRFEPSARI336 SAAAALRHPF346 LAKYHDPDDE356 PDCAPPFDFA 366 FDREALTRER376 IKEAIVAEIE386 DFHARREG
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| Ligand Name: 11-Cyclopentyl-2-[[2-Methoxy-4-[4-(4-Methylpiperazin-1-Yl)piperidin-1-Yl]carbonyl-Phenyl]amino]-5-Methyl-Pyrimido[4,5-B][1,4]benzodiazepin-6-One | Ligand Info | |||||
| Structure Description | Crystal Structure of MAPK7 (ERK5) with inhibitor | PDB:4B99 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [3] |
| PDB Sequence |
VTFDVGDEYE
56 IIETIGNGAY66 GVVSSARRRL76 TGQQVAIKKI86 PNAFDVVTNA96 KRTLRELKIL 106 KHFKHDNIIA116 IKDILRPTVP126 YGEFKSVYVV136 LDLMESDLHQ146 IIHSSQPLTL 156 EHVRYFLYQL166 LRGLKYMHSA176 QVIHRDLKPS186 NLLVNENCEL196 KIGDFGMARG 206 LQYFMTEYVA223 TRWYRAPELM233 LSLHEYTQAI243 DLWSVGCIFG253 EMLARRQLFP 263 GKNYVHQLQL273 IMMVLGTPSP283 AVIQRVRAYI298 QSLPPRQPVP308 WETVYPGADR 318 QALSLLGRML328 RFEPSARISA338 AAALRHPFLA348 KYHDPDDEPD358 CAPPFDFAFD 368 REALTRERIK378 EAIVAEIEDF388 HARRE
|
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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 .R4L or .R4L2 or .R4L3 or :3R4L;style chemicals stick;color identity;select .A:60 or .A:61 or .A:62 or .A:63 or .A:64 or .A:69 or .A:82 or .A:115 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:142 or .A:143 or .A:146 or .A:186 or .A:187 or .A:189 or .A:199 or .A:200; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR60
4.931
ILE61
3.455
GLY62
3.605
ASN63
3.667
GLY64
4.248
VAL69
3.374
ALA82
3.711
ILE115
3.402
LEU137
3.555
ASP138
3.566
LEU139
4.140
|
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| Ligand Name: Erk5-IN-2 | Ligand Info | |||||
| Structure Description | ERK5 in complex with a pyrrole inhibitor | PDB:5O7I | ||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | No | [4] |
| PDB Sequence |
EYEIIETIGN
63 GAYGVVSSAR73 RRLTGQQVAI83 KKIPNAFDVV93 TNAKRTLREL103 KILKHFKHDN 113 IIAIKDILRP123 TVPYGEFKSV133 YVVLDLMESD143 LHQIIHSSQP153 LTLEHVRYFL 163 YQLLRGLKYM173 HSAQVIHRDL183 KPSNLLVNEN193 CELKIGDFGM203 ARGLCTSPAE 213 HQYFMTEYVA223 TRWYRAPELM233 LSLHEYTQAI243 DLWSVGCIFG253 EMLARRQLFP 263 GKNYVHQLQL273 IMMVLGTPSP283 AVIQAVGAER293 VRAYIQSLPP303 RQPVPWETVY 313 PGADRQALSL323 LGRMLRFEPS333 ARISAAAALR343 HPFLAKYHDP353 DDEPDCAPPF 363 DFAFDREALT373 RERIKEAIVA383 EIEDFHARRE393
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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 .9N8 or .9N82 or .9N83 or :39N8;style chemicals stick;color identity;select .A:61 or .A:66 or .A:69 or .A:71 or .A:82 or .A:84 or .A:115 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:142 or .A:146 or .A:186 or .A:187 or .A:189 or .A:199 or .A:200; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: 4-({5-Fluoro-4-[2-Methyl-1-(Propan-2-Yl)-1h-Imidazol-5-Yl]pyrimidin-2-Yl}amino)-N-[2-(Piperidin-1-Yl)ethyl]benzamide | Ligand Info | |||||
| Structure Description | ERK5 in complex with small molecule | PDB:5BYZ | ||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [2] |
| PDB Sequence |
TFDVGDEYEI
57 IETIGNGAYG67 VVSSARRRLT77 GQQVAIKKIP87 NAFDVVTNAK97 RTLRELKILK 107 HFKHDNIIAI117 KDILRPTVPY127 GEFKSVYVVL137 DLMESDLHQI147 IHSSQPLTLE 157 HVRYFLYQLL167 RGLKYMHSAQ177 VIHRDLKPSN187 LLVNENCELK197 IGDFGMARGL 207 CTSPAEHQYF217 MTEYVATRWY227 RAPELMLSLH237 EYTQAIDLWS247 VGCIFGEMLA 257 RRQLFPGKNY267 VHQLQLIMMV277 LGTPSPAVIQ287 AVGAERVRAY297 IQSLPPRQPV 307 PWETVYPGAD317 RQALSLLGRM327 LRFEPSARIS337 AAAALRHPFL347 AKYHDPDDEP 357 DCAPPFDFAF367 DREALTRERI377 KEAIVAEIED387 FHARREGI
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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 .4WE or .4WE2 or .4WE3 or :34WE;style chemicals stick;color identity;select .A:61 or .A:62 or .A:63 or .A:66 or .A:69 or .A:82 or .A:84 or .A:102 or .A:115 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:142 or .A:143 or .A:145 or .A:146 or .A:186 or .A:187 or .A:189 or .A:199 or .A:200; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE61
3.282
GLY62
3.637
ASN63
4.667
TYR66
3.504
VAL69
3.862
ALA82
3.481
LYS84
2.938
GLU102
4.608
ILE115
3.392
LEU137
3.359
ASP138
3.162
LEU139
4.524
|
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| Ligand Name: 3-Amino-5-[(4-Chlorophenyl)amino]-N-(Propan-2-Yl)-1h-1,2,4-Triazole-1-Carboxamide | Ligand Info | |||||
| Structure Description | MITOGEN ACTIVATED PROTEIN KINASE 7 IN COMPLEX WITH INHIBITOR | PDB:4ZSG | ||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | No | [2] |
| PDB Sequence |
VTFDVGDEYE
56 IIETIGNGAY66 GVVSSARRRL76 TGQQVAIKKI86 PNAFDVVTNA96 KRTLRELKIL 106 KHFKHDNIIA116 IKDILRPTVP126 YGEFKSVYVV136 LDLMESDLHQ146 IIHSSQPLTL 156 EHVRYFLYQL166 LRGLKYMHSA176 QVIHRDLKPS186 NLLVNENCEL196 KIGDFGMARG 206 LCTSPAEHQY216 FMTEYVATRW226 YRAPELMLSL236 HEYTQAIDLW246 SVGCIFGEML 256 ARRQLFPGKN266 YVHQLQLIMM276 VLGTPSPAVI286 QAVGAERVRA296 YIQSLPPRQP 306 VPWETVYPGA316 DRQALSLLGR326 MLRFEPSARI336 SAAAALRHPF346 LAKYHDPDDE 356 PDCAPPFDFA366 FDREALTRER376 IKEAIVAEIE386 DFHARRE
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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 .4QX or .4QX2 or .4QX3 or :34QX;style chemicals stick;color identity;select .A:65 or .A:66 or .A:67 or .A:84 or .A:86 or .A:95 or .A:96 or .A:98 or .A:99 or .A:102 or .A:103 or .A:106 or .A:117 or .A:135 or .A:137 or .A:200; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: [4-(6,7-Dimethoxyquinazolin-4-yl)piperidin-1-yl]-[4-(trifluoromethyloxy)phenyl]methanone | Ligand Info | |||||
| Structure Description | Crystal structure of Compound 1 with ERK5 | PDB:6HKM | ||||
| Method | X-ray diffraction | Resolution | 2.47 Å | Mutation | No | [5] |
| PDB Sequence |
EYEIIETIGN
63 VVSSAQQVAI83 KKIPNAFDVV93 TNAKRTLREL103 KILKHFKHDN113 IIAIKDILRP 123 VPYGEFKSVY134 VVLDLMESDL144 HQIIHSSQPL154 TLEHVRYFLY164 QLLRGLKYMH 174 SAQVIHRDLK184 PSNLLVNENC194 ELKIGDFGMA204 RGLCTSEHQY216 FMTEYVATRW 226 YRAPELMLSL236 HEYTQAIDLW246 SVGCIFGEML256 ARRQLFPGKN266 YVHQLQLIMM 276 VLGTPSPAVI286 QAVGAERVRA296 YIQSLPQPVP308 WETVYPGADR318 QALSLLGRML 328 RFEPSARISA338 AAALRHPFLA348 KYHDPDDEPD358 CAPPFDFAFD368 REALTRERIK 378 EAIVAEIEDF388 HARREGI
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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 .G92 or .G922 or .G923 or :3G92;style chemicals stick;color identity;select .A:61 or .A:62 or .A:69 or .A:82 or .A:84 or .A:86 or .A:98 or .A:99 or .A:102 or .A:103 or .A:106 or .A:115 or .A:117 or .A:133 or .A:135 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:143 or .A:189 or .A:199 or .A:200 or .A:201; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE61
3.318
GLY62
4.241
VAL69
4.318
ALA82
3.417
LYS84
3.538
ILE86
3.263
ARG98
4.990
THR99
3.797
GLU102
3.266
LEU103
3.248
LEU106
3.527
ILE115
4.199
ILE117
4.181
|
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| Ligand Name: 3-Amino-5-[(4-Chloro-3-Methylphenyl)amino]-N-(Propan-2-Yl)-1h-1,2,4-Triazole-1-Carboxamide | Ligand Info | |||||
| Structure Description | MITOGEN ACTIVATED PROTEIN KINASE 7 IN COMPLEX WITH INHIBITOR | PDB:4ZSJ | ||||
| Method | X-ray diffraction | Resolution | 2.48 Å | Mutation | No | [2] |
| PDB Sequence |
DVGDEYEIIE
59 TIGNGAYGVV69 SSARRRLTGQ79 QVAIKKIPNA89 FDVVTNAKRT99 LRELKILKHF 109 KHDNIIAIKD119 ILRPTVPYGE129 FKSVYVVLDL139 MESDLHQIIH149 SSQPLTLEHV 159 RYFLYQLLRG169 LKYMHSAQVI179 HRDLKPSNLL189 VNENCELKIG199 DFGMARGLCT 209 SPAEHQYFMT219 EYVATRWYRA229 PELMLSLHEY239 TQAIDLWSVG249 CIFGEMLARR 259 QLFPGKNYVH269 QLQLIMMVLG279 TPSPAVIQAV289 GAERVRAYIQ299 SLPPRQPVPW 309 ETVYPGADRQ319 ALSLLGRMLR329 FEPSARISAA339 AALRHPFLAK349 YHDPDDEPDC 359 APPFDFAFDR369 EALTRERIKE379 AIVAEIEDFH389 ARRE
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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 .4R0 or .4R02 or .4R03 or :34R0;style chemicals stick;color identity;select .A:65 or .A:66 or .A:67 or .A:68 or .A:84 or .A:86 or .A:95 or .A:96 or .A:98 or .A:99 or .A:102 or .A:103 or .A:106 or .A:115 or .A:117 or .A:135 or .A:137 or .A:200; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: 3-Amino-5-[(4-Chlorophenyl)amino]-N-[(1s)-1-Phenylethyl]-1h-1,2,4-Triazole-1-Carboxamide | Ligand Info | |||||
| Structure Description | MITOGEN ACTIVATED PROTEIN KINASE 7 IN COMPLEX WITH INHIBITOR | PDB:4ZSL | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [2] |
| PDB Sequence |
DEYEIIETIG
62 NGAYGVVSSA72 RRRLTGQQVA82 IKKIPNAFDV92 VTNAKRTLRE102 LKILKHFKHD 112 NIIAIKDILR122 PTVPYGEFKS132 VYVVLDLMES142 DLHQIIHSSQ152 PLTLEHVRYF 162 LYQLLRGLKY172 MHSAQVIHRD182 LKPSNLLVNE192 NCELKIGDFG202 MARGLCTSPA 212 EHQYFMTEYV222 ATRWYRAPEL232 MLSLHEYTQA242 IDLWSVGCIF252 GEMLARRQLF 262 PGKNYVHQLQ272 LIMMVLGTPS282 PAVIQAVGAE292 RVRAYIQSLP302 PRQPVPWETV 312 YPGADRQALS322 LLGRMLRFEP332 SARISAAAAL342 RHPFLAKYHD352 PDDEPDCAPP 362 FDFAFDREAL372 TRERIKEAIV382 AEIEDFHARR392 E
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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 .4QZ or .4QZ2 or .4QZ3 or :34QZ;style chemicals stick;color identity;select .A:65 or .A:66 or .A:67 or .A:68 or .A:84 or .A:86 or .A:95 or .A:96 or .A:98 or .A:99 or .A:102 or .A:103 or .A:106 or .A:117 or .A:135 or .A:137; 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-Azanyl-4-(trifluoromethyloxy)phenyl]-[4-(7-methoxyquinazolin-4-yl)piperidin-1-yl]methanone | Ligand Info | |||||
| Structure Description | Crystal structure of Compound 35 with ERK5 | PDB:6HKN | ||||
| Method | X-ray diffraction | Resolution | 2.33 Å | Mutation | No | [5] |
| PDB Sequence |
EYEIIETIAY
66 GVVSSARRQQ80 VAIKKIPNAF90 DVVTNAKRTL100 RELKILKHFK110 HDNIIAIKDI 120 LRPTVPYGEF130 KSVYVVLDLM140 ESDLHQIIHS150 SQPLTLEHVR160 YFLYQLLRGL 170 KYMHSAQVIH180 RDLKPSNLLV190 NENCELKIGD200 FGMARGLCTS210 PAEHQYFMTE 220 YVATRWYRAP230 ELMLSLHEYT240 QAIDLWSVGC250 IFGEMLARRQ260 LFPGKNYVHQ 270 LQLIMMVLGT280 PSPAVIQAVG290 AERVRAYIQS300 LPPRQPVPWE310 TVYPGADRQA 320 LSLLGRMLRF330 EPSARISAAA340 ALRHPFLAKY350 HDPDDEPDCA360 PPFDFAFDRE 370 ALTRERIKEA380 IVAEIEDFHA390 RRE
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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 .G9E or .G9E2 or .G9E3 or :3G9E;style chemicals stick;color identity;select .A:61 or .A:66 or .A:69 or .A:82 or .A:84 or .A:86 or .A:99 or .A:102 or .A:103 or .A:106 or .A:115 or .A:117 or .A:133 or .A:135 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:142 or .A:143 or .A:189 or .A:199 or .A:200 or .A:201; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE61
3.228
TYR66
3.672
VAL69
4.306
ALA82
3.428
LYS84
3.400
ILE86
3.385
THR99
3.591
GLU102
3.127
LEU103
3.324
LEU106
3.609
ILE115
3.948
ILE117
4.147
VAL133
4.815
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module. J Biol Chem. 2013 Mar 22;288(12):8596-8609. | ||||
| REF 2 | Discovery of a novel allosteric inhibitor-binding site in ERK5: comparison with the canonical kinase hinge ATP-binding site. Acta Crystallogr D Struct Biol. 2016 May;72(Pt 5):682-93. | ||||
| REF 3 | X-ray crystal structure of ERK5 (MAPK7) in complex with a specific inhibitor. J Med Chem. 2013 Jun 13;56(11):4413-21. | ||||
| REF 4 | Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38Alpha and BRD4. Eur J Med Chem. 2019 Sep 15;178:530-543. | ||||
| REF 5 | Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2- d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5. J Med Chem. 2019 Jan 24;62(2):928-940. | ||||
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