Structure of PDB 4lwt Chain A Binding Site BS01

Receptor Information

>4lwt Chain A (length=86) Species: 8355 (Xenopus laevis)

MEKLVQPTPLLLSLLKSAGAQKETFTMKEVLYHLGQYIMAKQLYDEKQQH
IVHCSNDPLGELFGVQEFSVKEHRRIYAMISRNLVS

Ligand information

• Ligand ID: 20Q
• InChI: InChI=1S/C22H22Cl2N2O2/c1-14(27)26-9-3-5-16(13-26)22(12-15-4-2-6-17(23)10-15)19-8-7-18(24)11-20(19)25-21(22)28/h2,4,6-8,10-11,16H,3,5,9,12-13H2,1H3,(H,25,28)/t16-,22-/m0/s1
• InChIKey: RIBYLXUNNWIWJK-AOMKIAJQSA-N
• SMILES:
  OpenEye OEToolkits 1.7.6: CC(=O)N1CCCC(C1)C2(c3ccc(cc3NC2=O)Cl)Cc4cccc(c4)Cl
  OpenEye OEToolkits 1.7.6: CC(=O)N1CCC[C@@H](C1)[C@]2(c3ccc(cc3NC2=O)Cl)Cc4cccc(c4)Cl
  CACTVS 3.385: CC(=O)N1CCC[CH](C1)[C]2(Cc3cccc(Cl)c3)C(=O)Nc4cc(Cl)ccc24
  CACTVS 3.385: CC(=O)N1CCC[C@@H](C1)[C@]2(Cc3cccc(Cl)c3)C(=O)Nc4cc(Cl)ccc24
  ACDLabs 12.01: O=C(N4CCCC(C2(c1ccc(Cl)cc1NC2=O)Cc3cccc(Cl)c3)C4)C
• Formula: C22 H22 Cl2 N2 O2
• Name: (3S)-3-[(3R)-1-acetylpiperidin-3-yl]-6-chloro-3-(3-chlorobenzyl)-1,3-dihydro-2H-indol-2-one
• ZINC: ZINC000098208073
• PDB chain: 4lwt Chain A Residue 201

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4lwt Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.
• Resolution: 1.6 Å
• Binding residue (original residue number in PDB): L50 I57 Y63 V89 H92
• Binding residue (residue number reindexed from 1): L31 I38 Y44 V70 H73
• Annotation score: 1
• Binding affinity: MOAD: ic50=3.9uM
  PDBbind-CN: -logKd/Ki=5.41,IC50=3.9uM

Enzymatic activity

• Enzyme Commision number: 2.3.2.27: RING-type E3 ubiquitin transferase.

Gene Ontology

Biological Process

• GO:0043066 negative regulation of apoptotic process
• GO:0051726 regulation of cell cycle

Cellular Component

• GO:0005634 nucleus

External links

• PDB: RCSB:4lwt, PDBe:4lwt, PDBj:4lwt
• PDBsum: 4lwt
• PubMed: 24997575
• UniProt: P56273|MDM2_XENLA E3 ubiquitin-protein ligase Mdm2 (Gene Name=mdm2)