Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Ademetionine | Ligand Info | |||
| Canonical SMILES | C[S+](CCC(C(=O)[O-])N)CC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)O | ||||
| InChI | 1S/C15H22N6O5S/c1-27(3-2-7(16)15(24)25)4-8-10(22)11(23)14(26-8)21-6-20-9-12(17)18-5-19-13(9)21/h5-8,10-11,14,22-23H,2-4,16H2,1H3,(H2-,17,18,19,24,25)/t7-,8+,10+,11+,14+,27?/m0/s1 | ||||
| InChIKey | MEFKEPWMEQBLKI-AIRLBKTGSA-N | ||||
| PubChem Compound ID | 34755 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3QOW DOT1L Structure in complex with SAM | ||||||
| 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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| PDB ID: 1NW3 Structure of the Catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| 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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|
|
PRO133
3.209
GLU134
4.230
VAL135
3.783
TYR136
3.931
GLY137
2.890
GLU138
3.072
THR139
2.547
ASP161
3.255
LEU162
4.728
GLY163
2.772
SER164
3.737
GLY165
4.238
GLN168
2.977
|
|||||
| PDB ID: 7XCR Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 1:1 complex | ||||||
| Method | Electron microscopy | Resolution | 2.57 Å | Mutation | No | [3] |
| 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
|
|||||
|
|
PRO133
3.359
GLU134
3.797
VAL135
3.372
TYR136
4.143
GLY137
3.373
GLU138
3.592
THR139
3.204
ASP161
3.326
LEU162
4.864
GLY163
2.609
SER164
3.383
GLY165
3.797
GLN168
2.456
|
|||||
| PDB ID: 7XCT Cryo-EM structure of Dot1L and H2BK34ub-H3K79Nle nucleosome 2:1 complex | ||||||
| Method | Electron microscopy | Resolution | 2.72 Å | Mutation | No | [3] |
| 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 YFSSLK
|
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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 .SAM or .SAM2 or .SAM3 or :3SAM;style chemicals stick;color identity;select .K:133 or .K:134 or .K:135 or .K:136 or .K:137 or .K:138 or .K:139 or .K:161 or .K:162 or .K:163 or .K:164 or .K:165 or .K:168 or .K:169 or .K:185 or .K:186 or .K:187 or .K:188 or .K:191 or .K:221 or .K:222 or .K:223 or .K:224 or .K:239 or .K:241 or .K:245; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO133
3.145
GLU134
3.929
VAL135
3.655
TYR136
4.110
GLY137
3.337
GLU138
3.728
THR139
3.076
ASP161
3.349
LEU162
4.750
GLY163
2.793
SER164
3.375
GLY165
3.772
GLN168
2.467
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Chemogenetic analysis of human protein methyltransferases. Chem Biol Drug Des. 2011 Aug;78(2):199-210. | ||||
| REF 2 | Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell. 2003 Mar 7;112(5):711-23. | ||||
| REF 3 | H2B Lys34 Ubiquitination Induces Nucleosome Distortion to Stimulate Dot1L Activity. Nat Chem Biol. 2022 Sep;18(9):972-980. | ||||
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