Structure of PDB 4ekg Chain A Binding Site BS01

Receptor Information
>4ekg Chain A (length=319) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
LELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKLA
MENYDYDTKSFESMQRLCDKYNRAIDSIHQLWKGTTQPMKLNTRPSTGLL
RHILQQVYNHSVTDPEKLNSPEVYGETSFDLVAQMIDEIKMTDDDLFVDL
GSGVGQVVLQVAAATNCKHHYGVEKADIPAKYAETMDREFRKWMKWYGKK
HAEYTLERGDFLSEEWRERIANTSVIFVNNFAFGPEVDHQLKERFANMKE
GGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLKGSVSWTGKPVSY
YLHTIDRTILENYFSSLKN
Ligand information
Ligand ID0QJ
InChIInChI=1S/C25H36N8O4/c1-25(2,3)15-6-8-16(9-7-15)31-24(36)27-10-5-11-32(4)12-17-19(34)20(35)23(37-17)33-14-30-18-21(26)28-13-29-22(18)33/h6-9,13-14,17,19-20,23,34-35H,5,10-12H2,1-4H3,(H2,26,28,29)(H2,27,31,36)/t17-,19-,20-,23-/m1/s1
InChIKeyDHTNDMXCZIAPMX-ZDXOVATRSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)(C)c1ccc(cc1)NC(=O)NCCCN(C)CC2C(C(C(O2)n3cnc4c3ncnc4N)O)O
CACTVS 3.370CN(CCCNC(=O)Nc1ccc(cc1)C(C)(C)C)C[C@H]2O[C@H]([C@H](O)[C@@H]2O)n3cnc4c(N)ncnc34
OpenEye OEToolkits 1.7.6CC(C)(C)c1ccc(cc1)NC(=O)NCCCN(C)C[C@@H]2[C@H]([C@H]([C@@H](O2)n3cnc4c3ncnc4N)O)O
CACTVS 3.370CN(CCCNC(=O)Nc1ccc(cc1)C(C)(C)C)C[CH]2O[CH]([CH](O)[CH]2O)n3cnc4c(N)ncnc34
ACDLabs 12.01O=C(Nc1ccc(cc1)C(C)(C)C)NCCCN(C)CC4OC(n3cnc2c(ncnc23)N)C(O)C4O
FormulaC25 H36 N8 O4
Name5'-[(3-{[(4-tert-butylphenyl)carbamoyl]amino}propyl)(methyl)amino]-5'-deoxyadenosine
ChEMBLCHEMBL3087500
DrugBank
ZINCZINC000087613174
PDB chain4ekg Chain A Residue 500 [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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PDB4ekg Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L.
Resolution2.8 Å
Binding residue
(original residue number in PDB)		V135 Y136 D161 G163 E186 K187 D222 F223 F239 N241 S268 Y312
Binding residue
(residue number reindexed from 1)		V123 Y124 D149 G151 E174 K175 D210 F211 F227 N229 S256 Y300
Annotation score2
Binding affinityPDBbind-CN: -logKd/Ki=8.77,Kd=1.7nM
BindingDB: Ki=13nM
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
View graph for
Biological Process
External links
PDB RCSB:4ekg, PDBe:4ekg, PDBj:4ekg
PDBsum4ekg
PubMed22978415
UniProtQ8TEK3|DOT1L_HUMAN Histone-lysine N-methyltransferase, H3 lysine-79 specific (Gene Name=DOT1L)

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