Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T87686 | Target Info | |||
| Target Name | Histone-lysine N-methyltransferase (HLNM) | ||||
| Synonyms | Lysine N-methyltransferase 4; KMT4; KIAA1814; Histone-lysine N-methyltransferase, H3 lysine-79 specific; Histone H3-K79 methyltransferase; H3-K79-HMTase; DOT1-like protein | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | DOT1L | ||||
| Biochemical Class | Methyltransferase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Ademetionine | Ligand Info | |||||
| Structure Description | DOT1L Structure in complex with SAM | PDB:3QOW | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMENYLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTTQ94 PMKLNTRPST104 GLLRHILQQV 114 YNHSVTDPEK124 LNNYEPFSPE134 VYGETSFDLV144 AQMIDEIKMT154 DDDLFVDLGS 164 GVGQVVLQVA174 AATNCKHHYG184 VEKADIPAKY194 AETMDREFRK204 WMKWYGKKHA 214 EYTLERGDFL224 SEEWRERIAN234 TSVIFVNNFA244 FGPEVDHQLK254 ERFANMKEGG 264 RIVSSKPFAP274 LNFRINSRNL284 SDIGTIMRVV294 ELSPLKWTGK308 PVSYYLHTID 318 RTILENYFSS328 LK
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PRO133
3.163
GLU134
4.051
VAL135
3.296
TYR136
3.841
GLY137
3.180
GLU138
3.219
THR139
2.671
ASP161
2.866
LEU162
4.797
GLY163
2.742
SER164
3.661
GLY165
4.023
GLN168
3.000
VAL169
3.685
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Adenosine | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with adenosine and inhibitor CPD1 [N6-(2,6-dichlorophenyl)-N6-(pent-2-yn-1-yl)quinoline-4,6-diamine] | PDB:5MVS | ||||
| Method | X-ray diffraction | Resolution | 2.18 Å | Mutation | No | [2] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLNNYEP130 FSPEVYGETS140 FDLVAQMIDE150 IKMTDDDLFV160 DLGSGVGQVV 170 LQVAAATNCK180 HHYGVEKADI190 PAKYAETMDR200 EFRKWMKWYG210 KKHAEYTLER 220 GDFLSEEWRE230 RIANTSVIFV240 NNFAFGPEVD250 HQLKERFANM260 KEGGRIVSSK 270 PFAPLNFRIN280 SRNLSDIGTI290 MRVVELSPLK300 GSWTGKPVSY312 YLHTIDRTIL 322 ENYFSSLKNP332
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| Ligand Name: EPZ-5676 | Ligand Info | |||||
| Structure Description | Crystal Structure of DOT1L in Complex with EPZ-5676 | PDB:4HRA | ||||
| Method | X-ray diffraction | Resolution | 3.15 Å | Mutation | No | [3] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMENYVLIDY 63 DTKSFESMQR73 LCDKYNRAID83 SIHQLWKGTT93 QPMKLNTRPS103 TGLLRHILQQ 113 VYNHSVTDPE123 KLNNYEPTSF141 DLVAQMIDEI151 KMTDDDLFVD161 LGSGVGQVVL 171 QVAAATNCKH181 HYGVEKADIP191 AKYAETMDRE201 FRKWMKWYGK211 KHAEYTLERG 221 DFLSEEWRER231 IANTSVIFVN241 NFAFGPEVDH251 QLKERFANMK261 EGGRIVSSKP 271 FAPLNFRINS281 RNLSDIGTIM291 RVVELSPLKG301 SVGKPVSYYL314 HTIDRTILEN 324 YFSSLKNPKL334
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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 .EP6 or .EP62 or .EP63 or :3EP6;style chemicals stick;color identity;select .A:129 or .A:143 or .A:144 or .A:147 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:245 or .A:267 or .A:268 or .A:269 or .A:312; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU129
3.786
LEU143
4.000
VAL144
4.848
MET147
4.715
ASP161
2.791
LEU162
3.778
GLY163
3.231
SER164
3.084
GLY165
3.643
GLN168
3.869
VAL169
3.541
VAL185
3.325
GLU186
2.163
LYS187
3.194
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| Ligand Name: Norleucine | Ligand Info | |||||
| Structure Description | Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 1:1 complex | PDB:7XCR | ||||
| Method | Electron microscopy | Resolution | 2.57 Å | Mutation | No | [4] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTTQ94 PMKLNTRPST104 GLLRHILQQV 114 YNHSVTDPEK124 LNNYEPFSPE134 VYGETSFDLV144 AQMIDEIKMT154 DDDLFVDLGS 164 GVGQVVLQVA174 AATNCKHHYG184 VEKADIPAKY194 AETMDREFRK204 WMKWYGKKHA 214 EYTLERGDFL224 SEEWRERIAN234 TSVIFVNNFA244 FGPEVDHQLK254 ERFANMKEGG 264 RIVSSKPFAP274 LNFRINSRNL284 SDIGTIMRVV294 ELSPLKGSVS304 WTGKPVSYYL 314 HTIDRTILEN324 YFSSLKNP
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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 .NLE or .NLE2 or .NLE3 or :3NLE;style chemicals stick;color identity;select .K:128 or .K:135 or .K:136 or .K:137 or .K:241 or .K:243 or .K:244 or .K:305; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5'-iodotubercidin | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1l in complex with 5-iodotubercidin | PDB:3UWP | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [5] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMENYVLIDY 63 DTKSFESMQR73 LCDKYNRAID83 SIHQLWKGTT93 QPMKLNTRPS103 TGLLRHILQQ 113 VYNHSVTDPE123 KLNNYEPFSP133 EVYGETSFDL143 VAQMIDEIKM153 TDDDLFVDLG 163 SGVGQVVLQV173 AAATNCKHHY183 GVEKADIPAK193 YAETMDREFR203 KWMKWYGKKH 213 AEYTLERGDF223 LSEEWRERIA233 NTSVIFVNNF243 AFGPEVDHQL253 KERFANMKEG 263 GRIVSSKPFA273 PLNFRINSRN283 LSDIGTIMRV293 VELSPLKGSV303 SWTGKPVSYY 313 LHTIDRTILE323 NYFSSLKNPK333 LREEQEAARR343 R
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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 .5ID or .5ID2 or .5ID3 or :35ID;style chemicals stick;color identity;select .A:129 or .A:162 or .A:163 or .A:165 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:241 or .A:242 or .A:245 or .A:249; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5'-Deoxy-5'-(N,N-dimethylamino)adenosine | Ligand Info | |||||
| Structure Description | Crystal structure of DOT1L in complex with EPZ000004 | PDB:4EK9 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [6] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYDYDTKS 67 FESMQRLCDK77 YNRAIDSIHQ87 LWKGTTQPMK97 LNTRPSTGLL107 RHILQQVYNH 117 SVTDPEKLNN127 YEPFSPEVYG137 ETSFDLVAQM147 IDEIKMTDDD157 LFVDLGSGVG 167 QVVLQVAAAT177 NCKHHYGVEK187 ADIPAKYAET197 MDREFRKWMK207 WYGKKHAEYT 217 LERGDFLSEE227 WRERIANTSV237 IFVNNFAFGP247 EVDHQLKERF257 ANMKEGGRIV 267 SSKPFAPLNF277 RINSRNLSDI287 GTIMRVVELS297 PLKGSVSWTG307 KPVSYYLHTI 317 DRTILENYFS327 SLKNP
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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 .EP4 or .EP42 or .EP43 or :3EP4;style chemicals stick;color identity;select .A:133 or .A:134 or .A:135 or .A:136 or .A:137 or .A:162 or .A:163 or .A:164 or .A:165 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:241 or .A:245; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PRO133
3.175
GLU134
3.692
VAL135
3.477
TYR136
4.116
GLY137
3.141
LEU162
4.701
GLY163
3.209
SER164
4.864
GLY165
4.476
VAL185
3.738
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| Ligand Name: bromo-deaza-SAH | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1l in complex with a brominated SAH analog | PDB:3SX0 | ||||
| Method | X-ray diffraction | Resolution | 2.28 Å | Mutation | No | [7] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMEDYDTKSF 68 ESMQRLCDKY78 NRAIDSIHQL88 WKGTTQPMKL98 NTRPSTGLLR108 HILQQVYNHS 118 VTDPEKLNNY128 EPFSPEVYGE138 TSFDLVAQMI148 DEIKMTDDDL158 FVDLGSGVGQ 168 VVLQVAAATN178 CKHHYGVEKA188 DIPAKYAETM198 DREFRKWMKW208 YGKKHAEYTL 218 ERGDFLSEEW228 RERIANTSVI238 FVNNFAFGPE248 VDHQLKERFA258 NMKEGGRIVS 268 SKPFAPLNFR278 INSRNLSDIG288 TIMRVVELSP298 LKGSVSWTGK308 PVSYYLHTID 318 RTILENYFSS328 LKNP
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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 .SX0 or .SX02 or .SX03 or :3SX0;style chemicals stick;color identity;select .A:133 or .A:134 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:241 or .A:245 or .A:249; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PRO133
3.512
GLU134
4.122
VAL135
3.893
TYR136
3.864
GLY137
3.117
GLU138
3.352
THR139
2.508
ASP161
2.779
LEU162
4.618
GLY163
2.851
SER164
3.619
GLY165
4.011
GLN168
2.820
VAL169
3.793
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| Ligand Name: SGC0946 | Ligand Info | |||||
| Structure Description | Crystal structure of human DOT1L in complex with inhibitor SGC0946 | PDB:4ER6 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [5] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMENYVLIDY 63 DTKSFESMQR73 LCDKYNRAID83 SIHQLWKGTT93 QPMKLNTRPS103 TGLLRHILQQ 113 VYNHSVTDPE123 KLNPFSPEVY136 GETSFDLVAQ146 MIDEIKMTDD156 DLFVDLGSGV 166 GQVVLQVAAA176 TNCKHHYGVE186 KADIPAKYAE196 TMDREFRKWM206 KWYGKKHAEY 216 TLERGDFLSE226 EWRERIANTS236 VIFVNNFAFG246 PEVDHQLKER256 FANMKEGGRI 266 VSSKPFAPLN276 FRINSRNLSD286 IGTIMRVVEL296 SPLKGSVSWT306 GKPVSYYLHT 316 IDRTILENYF326 SSLKNPKLRE336 EQEAA
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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 .AW2 or .AW22 or .AW23 or :3AW2;style chemicals stick;color identity;select .A:126 or .A:143 or .A:144 or .A:147 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:166 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:242 or .A:245 or .A:249 or .A:267 or .A:268 or .A:269 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ASN126
4.759
LEU143
4.203
VAL144
4.573
MET147
3.859
ASP161
3.114
LEU162
3.844
GLY163
2.829
SER164
3.357
GLY165
3.472
VAL166
4.850
VAL169
3.375
VAL185
4.035
GLU186
2.436
LYS187
3.313
ALA188
3.614
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| Ligand Name: EPZ-004777 | Ligand Info | |||||
| Structure Description | Crystal Structure of Human DOT1L in complex with inhibitor EPZ004777 | PDB:4ER3 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [5] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMENYVLIDY 63 DTKSFESMQR73 LCDKYNRAID83 SIHQLWKGTT93 QPMKLNTRPS103 TGLLRHILQQ 113 VYNHSVTDPE123 KLNNETSFDL143 VAQMIDEIKM153 TDDDLFVDLG163 SGVGQVVLQV 173 AAATNCKHHY183 GVEKADIPAK193 YAETMDREFR203 KWMKWYGKKH213 AEYTLERGDF 223 LSEEWRERIA233 NTSVIFVNNF243 AFGPEVDHQL253 KERFANMKEG263 GRIVSSKPFA 273 PLNFRINSRN283 LSDIGTIMRV293 VELSPLKGSV310 SYYLHTIDRT320 ILENYFSSLK 330 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 .0QK or .0QK2 or .0QK3 or :30QK;style chemicals stick;color identity;select .A:143 or .A:144 or .A:147 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:243 or .A:245 or .A:267 or .A:268 or .A:269 or .A:312; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU143
3.950
VAL144
4.404
MET147
3.499
ASP161
3.047
LEU162
3.998
GLY163
2.775
SER164
3.533
GLY165
3.708
GLN168
4.144
VAL169
3.600
VAL185
3.788
GLU186
2.367
LYS187
3.274
ALA188
3.949
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5'-[(3-{[(4-Tert-Butylphenyl)carbamoyl]amino}propyl)(Methyl)amino]-5'-Deoxyadenosine | Ligand Info | |||||
| Structure Description | Crystal Structure of DOT1L in Complex with EPZ003696 | PDB:4EKG | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [6] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYDYDTKS 67 FESMQRLCDK77 YNRAIDSIHQ87 LWKGTTQPMK97 LNTRPSTGLL107 RHILQQVYNH 117 SVTDPEKLNS132 PEVYGETSFD142 LVAQMIDEIK152 MTDDDLFVDL162 GSGVGQVVLQ 172 VAAATNCKHH182 YGVEKADIPA192 KYAETMDREF202 RKWMKWYGKK212 HAEYTLERGD 222 FLSEEWRERI232 ANTSVIFVNN242 FAFGPEVDHQ252 LKERFANMKE262 GGRIVSSKPF 272 APLNFRINSR282 NLSDIGTIMR292 VVELSPLKGS302 VSWTGKPVSY312 YLHTIDRTIL 322 ENYFSSLKN
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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 .0QJ or .0QJ2 or .0QJ3 or :30QJ;style chemicals stick;color identity;select .A:135 or .A:136 or .A:137 or .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:245 or .A:267 or .A:268 or .A:269 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL135
3.637
TYR136
3.201
GLY137
4.470
SER140
4.506
LEU143
3.959
VAL144
4.538
MET147
3.573
ASP161
2.944
LEU162
4.576
GLY163
2.605
SER164
3.731
GLY165
3.858
GLN168
4.189
VAL169
3.803
VAL185
4.125
GLU186
2.522
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| Ligand Name: 5'-Deoxy-5'-[(3-{[(4-Methylphenyl)carbamoyl]amino}propyl)(Propan-2-Yl)amino]adenosine | Ligand Info | |||||
| Structure Description | Crystal structure of human DOT1L in complex with inhibitor FED2 | PDB:4EQZ | ||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [5] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MEYDTKSFES 70 MQRLCDKYNR80 AIDSIHQLWK90 GTTQPMKLNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLNNYEP130 FSPEVYGETS140 FDLVAQMIDE150 IKMTDDDLFV160 DLGSGVGQVV 170 LQVAAATNCK180 HHYGVEKADI190 PAKYAETMDR200 EFRKWMKWYG210 KKHAEYTLER 220 GDFLSEEWRE230 RIANTSVIFV240 NNFAFGPEVD250 HQLKERFANM260 KEGGRIVSSK 270 PFAPLNFRIN280 SRNLSDIGTI290 MRVVELSPLK300 GSVSWTGKPV310 SYYLHTIDRT 320 ILENYFSSLK330 NPKLREEQEA340 AR
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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 .AW0 or .AW02 or .AW03 or :3AW0;style chemicals stick;color identity;select .A:128 or .A:130 or .A:131 or .A:133 or .A:134 or .A:140 or .A:144 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:245 or .A:267 or .A:268 or .A:269 or .A:312; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TYR128
4.024
PRO130
3.605
PHE131
3.361
PRO133
4.097
GLU134
4.208
SER140
3.918
VAL144
4.203
ASP161
2.860
LEU162
4.097
GLY163
2.737
SER164
3.645
GLY165
3.581
GLN168
4.129
VAL169
3.514
VAL185
3.822
GLU186
2.573
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|||||
| Ligand Name: 5-Bromo-7-{5-[(3-{[(4-Tert-Butylphenyl)carbamoyl]amino}propyl)amino]-5-Deoxy-Beta-D-Ribofuranosyl}-7h-Pyrrolo[2,3-D]pyrimidin-4-Amine | Ligand Info | |||||
| Structure Description | Crystal Structure of human DOT1L in complex with inhibitor SGC0947 | PDB:4ER7 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [5] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMIDYDTKSF 68 ESMQRLCDKY78 NRAIDSIHQL88 WKGTTQPMKL98 NTRPSTGLLR108 HILQQVYNHS 118 VTDPEKLNNY128 EETSFDLVAQ146 MIDEIKMTDD156 DLFVDLGSGV166 GQVVLQVAAA 176 TNCKHHYGVE186 KADIPAKYAE196 TMDREFRKWM206 KWYGKKHAEY216 TLERGDFLSE 226 EWRERIANTS236 VIFVNNFAFG246 PEVDHQLKER256 FANMKEGGRI266 VSSKPFAPLN 276 FRINSRNLSD286 IGTIMRVVEL296 SPLKGSVSWT306 GKPVSYYLHT316 IDRTILENYF 326 SSLKNPKLRE336 EQEAAR
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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 .AW3 or .AW32 or .AW33 or :3AW3;style chemicals stick;color identity;select .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:245 or .A:249 or .A:267 or .A:268 or .A:269 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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SER140
4.636
LEU143
3.972
VAL144
4.138
MET147
3.770
ASP161
3.199
LEU162
4.835
GLY163
2.592
SER164
3.673
GLY165
3.849
GLN168
4.319
VAL169
3.441
VAL185
3.976
GLU186
2.378
LYS187
3.175
ALA188
3.849
|
|||||
| Ligand Name: (2~{s})-2-Azanyl-4-[[(2~{s},3~{s},4~{r},5~{r})-5-(4-Azanyl-5-Cyano-Pyrrolo[2,3-D]pyrimidin-7-Yl)-3,4-Bis(Oxidanyl)oxolan-2-Yl]methylsulfanyl]butanoic Acid | Ligand Info | |||||
| Structure Description | complex of Dot1l with SS148 | PDB:5JUW | ||||
| Method | X-ray diffraction | Resolution | 2.28 Å | Mutation | No | [8] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMENYDTKSF 68 ESMQRLCDKY78 NRAIDSIHQL88 WKGTTQPMKL98 NTRPSTGLLR108 HILQQVYNHS 118 VTDPEKLNNY128 EPFSPEVYGE138 TSFDLVAQMI148 DEIKMTDDDL158 FVDLGSGVGQ 168 VVLQVAAATN178 CKHHYGVEKA188 DIPAKYAETM198 DREFRKWMKW208 YGKKHAEYTL 218 ERGDFLSEEW228 RERIANTSVI238 FVNNFAFGPE248 VDHQLKERFA258 NMKEGGRIVS 268 SKPFAPLNFR278 INSRNLSDIG288 TIMRVVELSP298 LKGSVSWTGK308 PVSYYLHTID 318 RTILENYFSS328 LKNP
|
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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 .6NR or .6NR2 or .6NR3 or :36NR;style chemicals stick;color identity;select .A:133 or .A:134 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:241 or .A:245 or .A:249; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO133
3.343
GLU134
4.131
VAL135
3.704
TYR136
3.900
GLY137
3.136
GLU138
3.309
THR139
2.612
ASP161
2.725
LEU162
4.716
GLY163
2.746
SER164
3.552
GLY165
3.996
GLN168
2.958
VAL169
3.830
|
|||||
| Ligand Name: 5'-[(3-{[(4-Tert-Butylphenyl)carbamoyl]amino}propyl)(Propan-2-Yl)amino]-5'-Deoxyadenosine | Ligand Info | |||||
| Structure Description | Crystal Structure of human DOT1L in complex with inhibitor FED1 | PDB:4ER0 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [5] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMDYDTKSFE 69 SMQRLCDKYN79 RAIDSIHQLW89 KGTTQPMKLN99 TRPSTGLLRH109 ILQQVYNHSV 119 TDPETSFDLV144 AQMIDEIKMT154 DDDLFVDLGS164 GVGQVVLQVA174 AATNCKHHYG 184 VEKADIPAKY194 AETMDREFRK204 WMKWYGKKHA214 EYTLERGDFL224 SEEWRERIAN 234 TSVIFVNNFA244 FGPEVDHQLK254 ERFANMKEGG264 RIVSSKPFAP274 LNFRINSRNL 284 SDIGTIMRVV294 ELSPLKGSVS304 WTGKPVSYYL314 HTIDRTILEN324 YFSSLKNPKL 334 REEQE
|
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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 .AW1 or .AW12 or .AW13 or :3AW1;style chemicals stick;color identity;select .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:245 or .A:267 or .A:268 or .A:269 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
SER140
4.843
LEU143
3.981
VAL144
4.424
MET147
3.898
ASP161
3.162
LEU162
4.234
GLY163
2.817
SER164
3.831
GLY165
3.941
GLN168
3.956
VAL169
3.471
VAL185
4.067
GLU186
2.086
LYS187
3.418
|
|||||
| Ligand Name: (2s)-2-Azanyl-4-[[(2s,3s,4r,5r)-5-[6-(Methylamino)purin-9-Yl]-3,4-Bis(Oxidanyl)oxolan-2-Yl]methylsulfanyl]butanoic Acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Human DOT1L in Complex with a Selective Inhibitor | PDB:3SR4 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [9] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTTQ94 PMKLNTRPST104 GLLRHILQQV 114 YNHSVTDPEK124 LNNYEPFSPE134 VYGETSFDLV144 AQMIDEIKMT154 DDDLFVDLGS 164 GVGQVVLQVA174 AATNCKHHYG184 VEKADIPAKY194 AETMDREFRK204 WMKWYGKKHA 214 EYTLERGDFL224 SEEWRERIAN234 TSVIFVNNFA244 FGPEVDHQLK254 ERFANMKEGG 264 RIVSSKPFAP274 LNFRINSRNL284 SDIGTIMRVV294 ELSPLKGSVS304 WTGKPVSYYL 314 HTIDRTILEN324 YFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TT8 or .TT82 or .TT83 or :3TT8;style chemicals stick;color identity;select .A:133 or .A:134 or .A:135 or .A:136 or .A:137 or .A:138 or .A:139 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:241 or .A:245 or .A:249; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO133
3.288
GLU134
4.132
VAL135
3.913
TYR136
3.620
GLY137
3.218
GLU138
3.335
THR139
2.604
ASP161
2.909
LEU162
4.646
GLY163
2.817
SER164
3.543
GLY165
3.993
GLN168
2.748
VAL169
3.475
|
|||||
| Ligand Name: N-[4-(Acetylamino)butyl]-5'-[(3-{[(4-Tert-Butylphenyl)carbamoyl]amino}propyl)(Propan-2-Yl)amino]-5'-Deoxyadenosine | Ligand Info | |||||
| Structure Description | Structure-Guided DOT1L Probe Optimization by Label-Free Ligand Displacement | PDB:4WVL | ||||
| Method | X-ray diffraction | Resolution | 2.41 Å | Mutation | No | [10] |
| PDB Sequence |
KLELRLKSPV
13 GAEPAVYPWP23 LPVYDKHHDA33 AHEIIETIRW43 VCEEIPDLKL53 AMEDYDTKSF 68 ESMQRLCDKY78 NRAIDSIHQL88 WKGTTQPMKL98 NTRPSTGLLR108 HILQQVYNHS 118 VTDPEKLNNY128 GETSFDLVAQ146 MIDEIKMTDD156 DLFVDLGSGV166 GQVVLQVAAA 176 TNCKHHYGVE186 KADIPAKYAE196 TMDREFRKWM206 KWYGKKHAEY216 TLERGDFLSE 226 EWRERIANTS236 VIFVNNFAFG246 PEVDHQLKER256 FANMKEGGRI266 VSSKPFAPLN 276 FRINSRNLSD286 IGTIMRVVEL296 SPLKGSVSWT306 GKPVSYYLHT316 IDRTILENYF 326 SSLKNPKLRE336 EQEAARRRQQ346 R
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .3US or .3US2 or .3US3 or :33US;style chemicals stick;color identity;select .A:127 or .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:162 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:244 or .A:245 or .A:249 or .A:267 or .A:268 or .A:269 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASN127
4.626
SER140
4.859
LEU143
4.944
VAL144
4.119
MET147
3.716
ASP161
3.075
LEU162
3.557
GLY163
2.809
SER164
3.689
GLY165
3.687
GLN168
4.314
VAL169
3.464
VAL185
3.969
GLU186
2.458
LYS187
3.289
ALA188
4.069
|
|||||
| Ligand Name: 1-N-[(S)-(3-chlorophenyl)-pyridin-2-ylmethyl]-4-methylsulfonyl-2-N-pyrimidin-2-ylbenzene-1,2-diamine | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with an inhibitor (compound 3). | PDB:6TE6 | ||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | No | [11] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLNNYEP130 FSPEVYGETS140 FDLVAQMIDE150 IKMTDDDLFV160 DLGSGVGQVV 170 LQVAAATNCK180 HHYGVEKADI190 PAKYAETMDR200 EFRKWMKWYG210 KKHAEYTLER 220 GDFLSEEWRE230 RIANTSVIFV240 NNFAFGPEVD250 HQLKERFANM260 KEGGRIVSSK 270 PFAPLNFRIN280 SRNLSDIGTI290 MRVVELSPLK300 SWTGKPVSYY313 LHTIDRTILE 323 NYFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N4W or .N4W2 or .N4W3 or :3N4W;style chemicals stick;color identity;select .A:129 or .A:130 or .A:131 or .A:136 or .A:140 or .A:143 or .A:144 or .A:147 or .A:169 or .A:239 or .A:240 or .A:241 or .A:243 or .A:244 or .A:267 or .A:268 or .A:269 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU129
4.000
PRO130
3.583
PHE131
3.366
TYR136
3.752
SER140
3.564
LEU143
3.621
VAL144
3.962
MET147
3.662
VAL169
3.606
PHE239
3.434
VAL240
3.585
|
|||||
| Ligand Name: (3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD1 [N6-(2,6-dichlorophenyl)-N6-(pent-2-yn-1-yl)quinoline-4,6-diamine] and inhibitor CPD2 [(R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine] | PDB:5MW3 | ||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | No | [2] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLNNYEP130 FSPEVYGETS140 FDLVAQMIDE150 IKMTDDDLFV160 DLGSGVGQVV 170 LQVAAATNCK180 HHYGVEKADI190 PAKYAETMDR200 EFRKWMKWYG210 KKHAEYTLER 220 GDFLSEEWRE230 RIANTSVIFV240 NNFAFGPEVD250 HQLKERFANM260 KEGGRIVSSK 270 PFAPLNFRIN280 SRNLSDIGTI290 MRVVELSPLK300 SWTGKPVSYY313 LHTIDRTILE 323 NYFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5JT or .5JT2 or .5JT3 or :35JT;style chemicals stick;color identity;select .A:163 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:245 or .A:249; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: N~6~-(2,6-Dichlorophenyl)-N~6~-(Pent-2-Yn-1-Yl)quinoline-4,6-Diamine | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD1 [N6-(2,6-dichlorophenyl)-N6-(pent-2-yn-1-yl)quinoline-4,6-diamine] and inhibitor CPD2 [(R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine] | PDB:5MW3 | ||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | No | [2] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLNNYEP130 FSPEVYGETS140 FDLVAQMIDE150 IKMTDDDLFV160 DLGSGVGQVV 170 LQVAAATNCK180 HHYGVEKADI190 PAKYAETMDR200 EFRKWMKWYG210 KKHAEYTLER 220 GDFLSEEWRE230 RIANTSVIFV240 NNFAFGPEVD250 HQLKERFANM260 KEGGRIVSSK 270 PFAPLNFRIN280 SRNLSDIGTI290 MRVVELSPLK300 SWTGKPVSYY313 LHTIDRTILE 323 NYFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5JJ or .5JJ2 or .5JJ3 or :35JJ;style chemicals stick;color identity;select .A:130 or .A:131 or .A:136 or .A:139 or .A:140 or .A:143 or .A:144 or .A:147 or .A:169 or .A:239 or .A:240 or .A:241 or .A:267 or .A:268 or .A:269 or .A:310 or .A:311 or .A:312; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 2-[[2-chloro-3-(2-methylpyridin-3-yl)-1-benzothiophen-5-yl]carbamoylamino]-N-[3-[methyl-[(3R)-1-(5H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl]amino]propyl]acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD7 [N-(3-(((R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)(methyl)amino)propyl)-2-(3-(2-chloro-3-(2-methylpyridin-3-yl)benzo[b]thiophen-5-yl)ureido)acetamide] | PDB:5MW4 | ||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [2] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGNTR101 PSTGLLRHIL111 QQVYNHSVTD 121 PEKGETSFDL143 VAQMIDEIKM153 TDDDLFVDLG163 SGVGQVVLQV173 AAATNCKHHY 183 GVEKADIPAK193 YAETMDREFR203 KWMKWYGKKH213 AEYTLERGDF223 LSEEWRERIA 233 NTSVIFVNNF243 AFGPEVDHQL253 KERFANMKEG263 GRIVSSKPFA273 PLNFRINSRN 283 LSDIGTIMRV293 VELSPLKSWT306 GKPVSYYLHT316 IDRTILENYF326 SSLKN |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5JU or .5JU2 or .5JU3 or :35JU;style chemicals stick;color identity;select .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:163 or .A:164 or .A:165 or .A:166 or .A:168 or .A:169 or .A:185 or .A:186 or .A:187 or .A:188 or .A:191 or .A:221 or .A:222 or .A:223 or .A:224 or .A:239 or .A:240 or .A:241 or .A:245 or .A:249 or .A:267 or .A:268 or .A:269 or .A:310 or .A:311 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
SER140
2.860
LEU143
3.446
VAL144
3.602
MET147
3.765
ASP161
2.806
GLY163
2.974
SER164
3.433
GLY165
3.600
VAL166
4.728
GLN168
4.078
VAL169
3.418
VAL185
4.069
GLU186
2.912
LYS187
3.332
ALA188
4.321
PRO191
4.059
|
|||||
| Ligand Name: Dot1L-IN-4 | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with an inhibitor (compound 10). | PDB:6TEL | ||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [11] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYHDAAHEI37 IETIRWVCEE47 IPDLKLAMEN57 YVLIDYDTKS 67 FESMQRLCDK77 YNRAIDSIHQ87 LWKGNTRPST104 GLLRHILQQV114 YNHSVTDPNN 127 YEPFSPEVYG137 ETSFDLVAQM147 IDEIKMTDDD157 LFVDLGSGVG167 QVVLQVAAAT 177 NCKHHYGVEK187 ADIPAKYAET197 MDREFRKWMK207 WYGKKHAEYT217 LERGDFLSEE 227 WRERIANTSV237 IFVNNFAFGP247 EVDHQLKERF257 ANMKEGGRIV267 SSKPFAPLNF 277 RINSRNLSDI287 GTIMRVVELS297 PLKSWTGKPV310 SYYLHTIDRT320 ILENYFSSLK 330 NP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N4Z or .N4Z2 or .N4Z3 or :3N4Z;style chemicals stick;color identity;select .A:129 or .A:130 or .A:131 or .A:136 or .A:140 or .A:143 or .A:144 or .A:147 or .A:169 or .A:239 or .A:240 or .A:241 or .A:243 or .A:244 or .A:267 or .A:268 or .A:269 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU129
3.746
PRO130
3.314
PHE131
3.291
TYR136
4.144
SER140
3.570
LEU143
3.212
VAL144
3.497
MET147
3.404
VAL169
3.685
PHE239
3.384
VAL240
3.320
|
|||||
| Ligand Name: 4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD1 [4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide] | PDB:5DTM | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [12] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGNTR101 PSTGLLRHIL111 QQVYNHSVTD 121 PEKLNNYEPF131 SPEVYGETSF141 DLVAQMIDEI151 KMTDDDLFVD161 LGSGVGQVVL 171 QVAAATNCKH181 HYGVEKADIP191 AKYAETMDRE201 FRKWMKWYGK211 KHAEYTLERG 221 DFLSEEWRER231 IANTSVIFVN241 NFAFGPEVDH251 QLKERFANMK261 EGGRIVSSKP 271 FAPLNFRINS281 RNLSDIGTIM291 RVVELSPLKG301 SWTGKPVSYY313 LHTIDRTILE 323 NYFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5F4 or .5F42 or .5F43 or :35F4;style chemicals stick;color identity;select .A:130 or .A:131 or .A:140 or .A:143 or .A:144 or .A:147 or .A:239 or .A:240 or .A:241 or .A:243 or .A:267 or .A:268 or .A:269 or .A:311 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: Dot1L-IN-5 | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with an inhibitor (compound 11). | PDB:6TEN | ||||
| Method | X-ray diffraction | Resolution | 2.21 Å | Mutation | No | [11] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGNTR101 PSTGLLRHIL111 QQVYNHSVTD 121 PEKLNNYEPF131 SPEVYGETSF141 DLVAQMIDEI151 KMTDDDLFVD161 LGSGVGQVVL 171 QVAAATNCKH181 HYGVEKADIP191 AKYAETMDRE201 FRKWMKWYGK211 KHAEYTLERG 221 DFLSEEWRER231 IANTSVIFVN241 NFAFGPEVDH251 QLKERFANMK261 EGGRIVSSKP 271 FAPLNFRINS281 RNLSDIGTIM291 RVVELSPLKS304 WTGKPVSYYL314 HTIDRTILEN 324 YFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N5K or .N5K2 or .N5K3 or :3N5K;style chemicals stick;color identity;select .A:129 or .A:130 or .A:131 or .A:136 or .A:140 or .A:143 or .A:144 or .A:147 or .A:169 or .A:239 or .A:240 or .A:241 or .A:243 or .A:244 or .A:267 or .A:268 or .A:269 or .A:309 or .A:310 or .A:311 or .A:312 or .A:313; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU129
3.983
PRO130
3.298
PHE131
3.471
TYR136
4.271
SER140
3.495
LEU143
3.212
VAL144
3.587
MET147
3.361
VAL169
3.703
PHE239
3.372
VAL240
3.307
|
|||||
| Ligand Name: N~4~-Methyl-N~2~-[2-Methyl-1-(2-Phenoxyphenyl)-1h-Indol-6-Yl]pyrimidine-2,4-Diamine | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD11 [N4-methyl-N2-(2-methyl-1-(2-phenoxyphenyl)-1H-indol-6-yl)pyrimidine-2,4-diamine] | PDB:5DT2 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [13] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGNTR101 PSTGLLRHIL111 QQVYNHSVTD 121 PEPFSPEVYG137 ETSFDLVAQM147 IDEIKMTDDD157 LFVDLGSGVG167 QVVLQVAAAT 177 NCKHHYGVEK187 ADIPAKYAET197 MDREFRKWMK207 WYGKKHAEYT217 LERGDFLSEE 227 WRERIANTSV237 IFVNNFAFGP247 EVDHQLKERF257 ANMKEGGRIV267 SSKPFAPLNF 277 RINSRNLSDI287 GTIMRVVELS297 PLKSWTGKPV310 SYYLHTIDRT320 ILENYFSSLK 330 N
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5EV or .5EV2 or .5EV3 or :35EV;style chemicals stick;color identity;select .A:130 or .A:131 or .A:139 or .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:163 or .A:164 or .A:165 or .A:169 or .A:239 or .A:240 or .A:241 or .A:243 or .A:267 or .A:268 or .A:269 or .A:310 or .A:311 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO130
4.643
PHE131
3.524
THR139
4.301
SER140
3.557
LEU143
3.594
VAL144
3.781
MET147
3.415
ASP161
2.738
GLY163
3.855
SER164
3.590
GLY165
4.556
|
|||||
| Ligand Name: N-(2,6-Dichlorophenyl)-4-Methoxy-N-Methylquinolin-6-Amine | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD5 [N-(2,6-dichlorophenyl)-4-methoxy-N-methylquinolin-6-amine] | PDB:5DTR | ||||
| Method | X-ray diffraction | Resolution | 2.34 Å | Mutation | No | [12] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGNTR101 PSTGLLRHIL111 QQVYNHSVTD 121 PEKLNNYEPF131 SPEVYGETSF141 DLVAQMIDEI151 KMTDDDLFVD161 LGSGVGQVVL 171 QVAAATNCKH181 HYGVEKADIP191 AKYAETMDRE201 FRKWMKWYGK211 KHAEYTLERG 221 DFLSEEWRER231 IANTSVIFVN241 NFAFGPEVDH251 QLKERFANMK261 EGGRIVSSKP 271 FAPLNFRINS281 RNLSDIGTIM291 RVVELSPLKG301 SWTGKPVSYY313 LHTIDRTILE 323 NYFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5F7 or .5F72 or .5F73 or :35F7;style chemicals stick;color identity;select .A:130 or .A:131 or .A:139 or .A:140 or .A:143 or .A:144 or .A:147 or .A:239 or .A:240 or .A:241 or .A:267 or .A:268 or .A:269 or .A:310 or .A:311 or .A:312; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: 6'-Chloro-1,4-Dimethyl-5'-(2-Methyl-6-{[4-(Methylamino)pyrimidin-2-Yl]amino}-1h-Indol-1-Yl)-3,3'-Bipyridin-2(1h)-One | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD10 [6'-chloro-1,4-dimethyl-5'-(2-methyl-6-((4-(methylamino)pyrimidin-2-yl)amino)-1H-indol-1-yl)-[3,3'-bipyridin]-2(1H)-one] | PDB:5DSX | ||||
| Method | X-ray diffraction | Resolution | 2.41 Å | Mutation | No | [13] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLEPFSP133 EVYGETSFDL143 VAQMIDEIKM153 TDDDLFVDLG163 SGVGQVVLQV 173 AAATNCKHHY183 GVEKADIPAK193 YAETMDREFR203 KWMKWYGKKH213 AEYTLERGDF 223 LSEEWRERIA233 NTSVIFVNNF243 AFGPEVDHQL253 KERFANMKEG263 GRIVSSKPFA 273 PLNFRINSRN283 LSDIGTIMRV293 VELSPLKSWT306 GKPVSYYLHT316 IDRTILENYF 326 SSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5EW or .5EW2 or .5EW3 or :35EW;style chemicals stick;color identity;select .A:131 or .A:136 or .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:163 or .A:164 or .A:165 or .A:168 or .A:169 or .A:239 or .A:240 or .A:241 or .A:243 or .A:267 or .A:268 or .A:269 or .A:310 or .A:311 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE131
3.404
TYR136
4.391
SER140
2.803
LEU143
3.726
VAL144
3.516
MET147
3.930
ASP161
2.697
GLY163
3.890
SER164
3.521
GLY165
4.585
GLN168
4.958
|
|||||
| Ligand Name: N-[1-(2-Chlorophenyl)-1h-Indol-6-Yl]-2-{[5-(2-Chlorophenyl)-1h-Tetrazol-1-Yl]acetyl}hydrazinecarboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD3 [N-(1-(2-chlorophenyl)-1H-indol-6-yl)-2-(2-(5-(2-chlorophenyl)-1H-tetrazol-1-yl)acetyl)hydrazinecarboxamide] | PDB:5DRY | ||||
| Method | X-ray diffraction | Resolution | 2.41 Å | Mutation | No | [13] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLNNYEP130 FSPEVYGETS140 FDLVAQMIDE150 IKMTDDDLFV160 DLGSGVGQVV 170 LQVAAATNCK180 HHYGVEKADI190 PAKYAETMDR200 EFRKWMKWYG210 KKHAEYTLER 220 GDFLSEEWRE230 RIANTSVIFV240 NNFAFGPEVD250 HQLKERFANM260 KEGGRIVSSK 270 PFAPLNFRIN280 SRNLSDIGTI290 MRVVELSPLK300 SWTGKPVSYY313 LHTIDRTILE 323 NYFSSLKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5EK or .5EK2 or .5EK3 or :35EK;style chemicals stick;color identity;select .A:131 or .A:132 or .A:133 or .A:136 or .A:140 or .A:143 or .A:144 or .A:147 or .A:161 or .A:163 or .A:164 or .A:165 or .A:166 or .A:167 or .A:168 or .A:169 or .A:239 or .A:240 or .A:241 or .A:267 or .A:268 or .A:269 or .A:312; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE131
3.370
SER132
4.114
PRO133
3.258
TYR136
3.542
SER140
3.564
LEU143
3.679
VAL144
3.315
MET147
3.537
ASP161
2.932
GLY163
2.977
SER164
3.335
GLY165
3.557
|
|||||
| Ligand Name: (2,6-Dichlorophenyl)(Quinolin-6-Yl)methanone | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD3 [(2,6-dichlorophenyl)(quinolin-6-yl)methanone] | PDB:5DTQ | ||||
| Method | X-ray diffraction | Resolution | 2.61 Å | Mutation | No | [12] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGTNT100 RPSTGLLRHI110 LQQVYNHSVT 120 DPEKLNNYEP130 FSPEVYGETS140 FDLVAQMIDE150 IKMTDDDLFV160 DLGSGVGQVV 170 LQVAAATNCK180 HHYGVEKADI190 PAKYAETMDR200 EFRKWMKWYG210 KKHAEYTLER 220 GDFLSEEWRE230 RIANTSVIFV240 NNFAFGPEVD250 HQLKERFANM260 KEGGRIVSSK 270 PFAPLNFRIN280 SRNLSDIGTI290 MRVVELSPLK300 GSWTGKPVSY312 YLHTIDRTIL 322 ENYFSSLKNP332
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5F6 or .5F62 or .5F63 or :35F6;style chemicals stick;color identity;select .A:130 or .A:131 or .A:140 or .A:143 or .A:144 or .A:147 or .A:239 or .A:240 or .A:241 or .A:243 or .A:267 or .A:268 or .A:269 or .A:311 or .A:312; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 2-({5-[(2-Chlorophenoxy)methyl]-1h-Tetrazol-1-Yl}acetyl)-N-(4-Chlorophenyl)hydrazinecarboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of Dot1L in complex with inhibitor CPD2 [2-(2-(5-((2-chlorophenoxy)methyl)-1H-tetrazol-1-yl)acetyl)-N-(4-chlorophenyl)hydrazinecarboxamide] | PDB:5DRT | ||||
| Method | X-ray diffraction | Resolution | 2.69 Å | Mutation | No | [13] |
| PDB Sequence |
LELRLKSPVG
14 AEPAVYPWPL24 PVYDKHHDAA34 HEIIETIRWV44 CEEIPDLKLA54 MENYVLIDYD 64 TKSFESMQRL74 CDKYNRAIDS84 IHQLWKGNTR101 PSTGLLRHIL111 QQVYNHSVTD 121 PEKLFSPEVY136 GETSFDLVAQ146 MIDEIKMTDD156 DLFVDLGSGV166 GQVVLQVAAA 176 TNCKHHYGVE186 KADIPAKYAE196 TMDREFRKWM206 KWYGKKHAEY216 TLERGDFLSE 226 EWRERIANTS236 VIFVNNFAFG246 PEVDHQLKER256 FANMKEGGRI266 VSSKPFAPLN 276 FRINSRNLSD286 IGTIMRVVEL296 SPLKGSWTGK308 PVSYYLHTID318 RTILENYFSS 328 LKNP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5EG or .5EG2 or .5EG3 or :35EG;style chemicals stick;color identity;select .A:131 or .A:132 or .A:133 or .A:136 or .A:140 or .A:144 or .A:147 or .A:161 or .A:163 or .A:164 or .A:165 or .A:166 or .A:167 or .A:168 or .A:169 or .A:239 or .A:240 or .A:241 or .A:267 or .A:268 or .A:269 or .A:312; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE131
3.201
SER132
4.423
PRO133
3.286
TYR136
3.790
SER140
3.500
VAL144
4.090
MET147
3.947
ASP161
2.918
GLY163
2.834
SER164
3.290
GLY165
3.492
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Chemogenetic analysis of human protein methyltransferases. Chem Biol Drug Des. 2011 Aug;78(2):199-210. | ||||
| REF 2 | Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach. ACS Med Chem Lett. 2017 Feb 14;8(3):338-343. | ||||
| REF 3 | Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013 Aug 8;122(6):1017-25. | ||||
| REF 4 | H2B Lys34 Ubiquitination Induces Nucleosome Distortion to Stimulate Dot1L Activity. Nat Chem Biol. 2022 Sep;18(9):972-980. | ||||
| REF 5 | Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun. 2012;3:1288. | ||||
| REF 6 | Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L. Chem Biol Drug Des. 2012 Dec;80(6):971-80. | ||||
| REF 7 | Bromo-deaza-SAH: a potent and selective DOT1L inhibitor. Bioorg Med Chem. 2013 Apr 1;21(7):1787-94. | ||||
| REF 8 | Complex of Dot1l with SS148 | ||||
| REF 9 | Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies. J Am Chem Soc. 2011 Oct 26;133(42):16746-9. | ||||
| REF 10 | Structure-guided DOT1L probe optimization by label-free ligand displacement. ACS Chem Biol. 2015 Mar 20;10(3):667-74. | ||||
| REF 11 | New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse. ACS Med Chem Lett. 2019 Dec 4;10(12):1655-1660. | ||||
| REF 12 | Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket. ACS Med Chem Lett. 2016 Jun 6;7(8):730-4. | ||||
| REF 13 | Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach. ACS Med Chem Lett. 2016 Jun 1;7(8):735-40. | ||||
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