Structure of PDB 4rn2 Chain B Binding Site BS01

Receptor Information
>4rn2 Chain B (length=357) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VPVYIYSPEYVSMCDSLAKIPKRADMVHSLIEAYALHKQMRIVKPKVASM
EEMATFHTDAYLQHLQKVSQEGSIEYGLGYDCPATEGIFDYAAAIGGATI
TAAQCLIDGMCKVAINWSGGWHHAKKDEASGFCYLNDAVLGILRLRRKFE
RILYVDLDLHHGDGVEDAFSFTSKVMTVSLHKFSPGFFPGTGDVSDVGLG
KGRYYSVNVPIQDGIQDEKYYQICESVLKEVYQAFNPKAVVLQLGADTIA
GDPMCSFNMTPVGIGKCLKYILQWQLATLILGGGGYNLANTARCWTYLTG
VILGKTLSSEIPDHEFFTAYGPDYVLEITPSCRPDRNEPHRIQQILNYIK
GNLKHVV
Ligand information
Ligand IDL7G
InChIInChI=1S/C23H31N5O3S2/c1-14(2)19-20(30)26-16(6-4-5-9-32)11-18(29)25-12-17-10-15(7-8-24-17)21-28-23(3,13-33-21)22(31)27-19/h4,6-8,10,14,16,19,32H,5,9,11-13H2,1-3H3,(H,25,29)(H,26,30)(H,27,31)/b6-4+/t16-,19+,23+/m1/s1
InChIKeyKTHSULHRWFVWHD-GZGVDZSUSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CC(C)[CH]1NC(=O)[C]2(C)CSC(=N2)c3ccnc(CNC(=O)C[CH](NC1=O)C=CCCS)c3
CACTVS 3.385CC(C)[C@@H]1NC(=O)[C@]2(C)CSC(=N2)c3ccnc(CNC(=O)C[C@H](NC1=O)/C=C/CCS)c3
OpenEye OEToolkits 1.7.6CC(C)[C@H]1C(=O)N[C@@H](CC(=O)NCc2cc(ccn2)C3=N[C@@](CS3)(C(=O)N1)C)/C=C/CCS
OpenEye OEToolkits 1.7.6CC(C)C1C(=O)NC(CC(=O)NCc2cc(ccn2)C3=NC(CS3)(C(=O)N1)C)C=CCCS
ACDLabs 12.01O=C2NCc1nccc(c1)C3=NC(C(=O)NC(C(=O)NC(/C=C/CCS)C2)C(C)C)(C)CS3
FormulaC23 H31 N5 O3 S2
Name(5R,8S,11S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-3-thia-7,10,14,17,21-pentaazatricyclo[14.3.1.1~2,5~]henicosa-1(20),2(21),16,18-tetraene-6,9,13-trione
ChEMBLCHEMBL3593415
DrugBank
ZINCZINC000230838965
PDB chain4rn2 Chain A Residue 404 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4rn2 Variable Active Site Loop Conformations Accommodate the Binding of Macrocyclic Largazole Analogues to HDAC8.
Resolution2.39 Å
Binding residue
(original residue number in PDB)		P273 Y306
Binding residue
(residue number reindexed from 1)		P253 Y286
Annotation score1
Binding affinityMOAD: ic50=1500nM
BindingDB: IC50=1491nM
Enzymatic activity
Enzyme Commision number 3.5.1.-
3.5.1.98: histone deacetylase.
Gene Ontology
Molecular Function
GO:0004407 histone deacetylase activity
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0030544 Hsp70 protein binding
GO:0033558 protein lysine deacetylase activity
GO:0046872 metal ion binding
GO:0051879 Hsp90 protein binding
GO:0140297 DNA-binding transcription factor binding
GO:0160008 protein decrotonylase activity
GO:0160009 histone decrotonylase activity
Biological Process
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0006325 chromatin organization
GO:0007064 mitotic sister chromatid cohesion
GO:0031397 negative regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0032204 regulation of telomere maintenance
GO:0040029 epigenetic regulation of gene expression
Cellular Component
GO:0000118 histone deacetylase complex
GO:0000228 nuclear chromosome
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005737 cytoplasm

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Molecular Function
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Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4rn2, PDBe:4rn2, PDBj:4rn2
PDBsum4rn2
PubMed25793284
UniProtQ9BY41|HDAC8_HUMAN Histone deacetylase 8 (Gene Name=HDAC8)

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