Structure of PDB 5u8a Chain A Binding Site BS01

Receptor Information

>5u8a Chain A (length=358) Species: 9606 (Homo sapiens)

FKCVNSLKEDHNQPLFGVQFNWHSKEGDPLVFATVGSNRVTLYECHSQGE
IRLLQSYVDADADENFYTCAWTYDSNTSHPLLAVAGSRGIIRIINPITMQ
CIKHYVGHGNAINELKFHPRDPNLLLSVSKDHALRLWNIQTDTLVAIFGG
VEGHRDEVLSADYDLLGEKIMSCGMDHSLKLWRINSKRMMNAIKESYDYN
PNKTNRPFISQKIHFPDFSTRDIHRNYVDCVRWLGDLILSKSCENAIVCW
KPGKMEDDIDKIKPSESNVTILGRFDYSQCDIWYMRFSMDFWQKMLALGN
QVGKLYVWDLEVEDPHKAKCTTLTHHKCGAAIRQTSFSRDSSILIAVCDD
ASIWRWDR

Ligand information

• Ligand ID: 82D
• InChI: InChI=1S/C22H25BrFN3/c1-25(2)22-14-27(13-18-19(23)8-6-9-20(18)24)12-17(22)16-11-26(3)21-10-5-4-7-15(16)21/h4-11,17,22H,12-14H2,1-3H3/t17-,22+/m1/s1
• InChIKey: ZNFRUVZPVKADAA-VGSWGCGISA-N
• SMILES:
  CACTVS 3.385: CN(C)[CH]1CN(C[CH]1c2cn(C)c3ccccc23)Cc4c(F)cccc4Br
  CACTVS 3.385: CN(C)[C@H]1CN(C[C@@H]1c2cn(C)c3ccccc23)Cc4c(F)cccc4Br
  OpenEye OEToolkits 2.0.6: Cn1cc(c2c1cccc2)[C@H]3CN(C[C@@H]3N(C)C)Cc4c(cccc4Br)F
  OpenEye OEToolkits 2.0.6: Cn1cc(c2c1cccc2)C3CN(CC3N(C)C)Cc4c(cccc4Br)F
  ACDLabs 12.01: c12c(cccc1)n(cc2C4CN(Cc3c(Br)cccc3F)CC4N(C)C)C
• Formula: C22 H25 Br F N3
• Name: (3R,4S)-1-[(2-bromo-6-fluorophenyl)methyl]-N,N-dimethyl-4-(1-methyl-1H-indol-3-yl)pyrrolidin-3-amine
• ChEMBL: CHEMBL4075197
• PDB chain: 5u8a Chain A Residue 501

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5u8a SAR of amino pyrrolidines as potent and novel protein-protein interaction inhibitors of the PRC2 complex through EED binding.
• Resolution: 1.45 Å
• Binding residue (original residue number in PDB): F97 Y148 E238 L240 D310 Y365 R367 R414
• Binding residue (residue number reindexed from 1): F16 Y67 E157 L159 D229 Y284 R286 R333
• Annotation score: 1
• Binding affinity: MOAD: Ki=13nM
  PDBbind-CN: -logKd/Ki=7.89,Ki=13nM
  BindingDB: Kd=90nM,Ki=13nM,IC50=8300nM

External links

• PDB: RCSB:5u8a, PDBe:5u8a, PDBj:5u8a
• PDBsum: 5u8a
• PubMed: 28254486
• UniProt: O75530|EED_HUMAN Polycomb protein EED (Gene Name=EED)