Structure of PDB 4hra Chain A Binding Site BS01

Receptor Information
>4hra Chain A (length=320) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KLELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKL
AMENYVLIDYDTKSFESMQRLCDKYNRAIDSIHQLWKGTTQPMKLNTRPS
TGLLRHILQQVYNHSVTDPEKLNNYEPTSFDLVAQMIDEIKMTDDDLFVD
LGSGVGQVVLQVAAATNCKHHYGVEKADIPAKYAETMDREFRKWMKWYGK
KHAEYTLERGDFLSEEWRERIANTSVIFVNNFAFGPEVDHQLKERFANMK
EGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLKGSVGKPVSYYL
HTIDRTILENYFSSLKNPKL
Ligand information
Ligand IDEP6
InChIInChI=1S/C30H42N8O3/c1-16(2)37(13-22-25(39)26(40)29(41-22)38-15-34-24-27(31)32-14-33-28(24)38)19-10-17(11-19)6-9-23-35-20-8-7-18(30(3,4)5)12-21(20)36-23/h7-8,12,14-17,19,22,25-26,29,39-40H,6,9-11,13H2,1-5H3,(H,35,36)(H2,31,32,33)/t17-,19+,22-,25-,26-,29-/m1/s1
InChIKeyLXFOLMYKSYSZQS-LURJZOHASA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)N(CC1C(C(C(O1)n2cnc3c2ncnc3N)O)O)C4CC(C4)CCc5[nH]c6ccc(cc6n5)C(C)(C)C
CACTVS 3.370CC(C)N(C[CH]1O[CH]([CH](O)[CH]1O)n2cnc3c(N)ncnc23)[CH]4C[CH](CCc5[nH]c6ccc(cc6n5)C(C)(C)C)C4
OpenEye OEToolkits 1.7.6CC(C)N(C[C@@H]1[C@H]([C@H]([C@@H](O1)n2cnc3c2ncnc3N)O)O)C4CC(C4)CCc5[nH]c6ccc(cc6n5)C(C)(C)C
CACTVS 3.370CC(C)N(C[C@H]1O[C@H]([C@H](O)[C@@H]1O)n2cnc3c(N)ncnc23)[C@H]4C[C@@H](CCc5[nH]c6ccc(cc6n5)C(C)(C)C)C4
ACDLabs 12.01n2c1c(ncnc1n(c2)C3OC(C(O)C3O)CN(C(C)C)C6CC(CCc5nc4cc(ccc4n5)C(C)(C)C)C6)N
FormulaC30 H42 N8 O3
Name5'-[{cis-3-[2-(5-tert-butyl-1H-benzimidazol-2-yl)ethyl]cyclobutyl}(propan-2-yl)amino]-5'-deoxyadenosine
ChEMBLCHEMBL3414626
DrugBankDB12920
ZINCZINC000168212088
PDB chain4hra Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB4hra Potent inhibition of DOT1L as treatment of MLL-fusion leukemia.
Resolution3.15 Å
Binding residue
(original residue number in PDB)		D161 G163 S164 V169 V185 E186 K187 G221 D222 F223 F239 N241
Binding residue
(residue number reindexed from 1)		D150 G152 S153 V158 V174 E175 K176 G210 D211 F212 F228 N230
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=10.10,Ki=0.08nM
BindingDB: Ki=0.080000nM,IC50=<0.100000nM
Enzymatic activity
Enzyme Commision number 2.1.1.360: [histone H3]-lysine(79) N-trimethyltransferase.
Gene Ontology
Molecular Function
GO:0031151 histone H3K79 methyltransferase activity
Biological Process
GO:0051726 regulation of cell cycle

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Molecular Function
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Biological Process
External links
PDB RCSB:4hra, PDBe:4hra, PDBj:4hra
PDBsum4hra
PubMed23801631
UniProtQ8TEK3|DOT1L_HUMAN Histone-lysine N-methyltransferase, H3 lysine-79 specific (Gene Name=DOT1L)

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