Structure of PDB 4eki Chain A Binding Site BS01

Receptor Information
>4eki 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]
KLELRLKSPVGAEPAVYPWPLPVYDKHHDAAHEIIETIRWVCEEIPDLKL
AMENYDYDTKSFESMQRLCDKYNRAIDSIHQLWKGTTQPMKLNTRPSTGL
LRHILQQVYNHSVTDPEKLNSPEVYGETSFDLVAQMIDEIKMTDDDLFVD
LGSGVGQVVLQVAAATNCKHHYGVEKADIPAKYAETMDREFRKWMKWYGK
KHAEYTLERGDFLSEEWRERIANTSVIFVNNFAFGPEVDHQLKERFANMK
EGGRIVSSKPFAPLNFRINSRNLSDIGTIMRVVELSPLKGSVSWTGKPVS
YYLHTIDRTILENYFSSLK
Ligand information
Ligand ID0QK
InChIInChI=1S/C28H41N7O4/c1-17(2)34(13-6-12-30-27(38)33-19-9-7-18(8-10-19)28(3,4)5)15-21-22(36)23(37)26(39-21)35-14-11-20-24(29)31-16-32-25(20)35/h7-11,14,16-17,21-23,26,36-37H,6,12-13,15H2,1-5H3,(H2,29,31,32)(H2,30,33,38)/t21-,22-,23-,26-/m1/s1
InChIKeyWXRGFPHDRFQODR-ICLZECGLSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)N(CCCNC(=O)Nc1ccc(cc1)C(C)(C)C)CC2C(C(C(O2)n3ccc4c3ncnc4N)O)O
OpenEye OEToolkits 1.7.6CC(C)N(CCCNC(=O)Nc1ccc(cc1)C(C)(C)C)C[C@@H]2[C@H]([C@H]([C@@H](O2)n3ccc4c3ncnc4N)O)O
CACTVS 3.370CC(C)N(CCCNC(=O)Nc1ccc(cc1)C(C)(C)C)C[CH]2O[CH]([CH](O)[CH]2O)n3ccc4c(N)ncnc34
CACTVS 3.370CC(C)N(CCCNC(=O)Nc1ccc(cc1)C(C)(C)C)C[C@H]2O[C@H]([C@H](O)[C@@H]2O)n3ccc4c(N)ncnc34
ACDLabs 12.01O=C(Nc1ccc(cc1)C(C)(C)C)NCCCN(C(C)C)CC4OC(n3ccc2c(ncnc23)N)C(O)C4O
FormulaC28 H41 N7 O4
Name7-{5-[(3-{[(4-tert-butylphenyl)carbamoyl]amino}propyl)(propan-2-yl)amino]-5-deoxy-beta-D-ribofuranosyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine
ChEMBLCHEMBL2169919
DrugBank
ZINCZINC000089469833
PDB chain4eki 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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PDB4eki Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L.
Resolution2.85 Å
Binding residue
(original residue number in PDB)		L143 D161 G163 S164 V169 E186 K187 D222 F223 N241
Binding residue
(residue number reindexed from 1)		L132 D150 G152 S153 V158 E175 K176 D211 F212 N230
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=10.00,Kd=0.10nM
BindingDB: Ki=0.300000nM,IC50=0.400000nM,EC50=9.0nM,Kd=0.250000nM
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:4eki, PDBe:4eki, PDBj:4eki
PDBsum4eki
PubMed22978415
UniProtQ8TEK3|DOT1L_HUMAN Histone-lysine N-methyltransferase, H3 lysine-79 specific (Gene Name=DOT1L)

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