Structure of PDB 5lav Chain A Binding Site BS01

Receptor Information

>5lav Chain A (length=93) Species: 9606 (Homo sapiens)

IPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYD
EKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVN

Ligand information

• Ligand ID: 6SK
• InChI: InChI=1S/C22H25Cl2N3O/c1-21(2,3)12-27-11-17(25)19(13-5-4-6-14(23)9-13)22(27)16-8-7-15(24)10-18(16)26-20(22)28/h4-10,17,19H,11-12,25H2,1-3H3,(H,26,28)/t17-,19+,22-/m1/s1
• InChIKey: CWDGHXCEKKZGEC-ZWCUEREDSA-N
• SMILES:
  CACTVS 3.385: CC(C)(C)CN1C[C@@H](N)[C@H](c2cccc(Cl)c2)[C@]13C(=O)Nc4cc(Cl)ccc34
  CACTVS 3.385: CC(C)(C)CN1C[CH](N)[CH](c2cccc(Cl)c2)[C]13C(=O)Nc4cc(Cl)ccc34
  OpenEye OEToolkits 2.0.5: CC(C)(C)CN1CC(C(C12c3ccc(cc3NC2=O)Cl)c4cccc(c4)Cl)N
  OpenEye OEToolkits 2.0.5: CC(C)(C)CN1C[C@H]([C@@H]([C@@]12c3ccc(cc3NC2=O)Cl)c4cccc(c4)Cl)N
• Formula: C22 H25 Cl2 N3 O
• Name: (3~{S},3'~{S},4'~{S})-4'-azanyl-6-chloranyl-3'-(3-chlorophenyl)-1'-(2,2-dimethylpropyl)spiro[1~{H}-indole-3,2'-pyrrolidine]-2-one
• ChEMBL: CHEMBL4785458
• ZINC: ZINC000584904931
• PDB chain: 5lav Chain A Residue 201

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5lav Discovery of Novel Spiro[3H-indole-3,2'-pyrrolidin]-2(1H)-one Compounds as Chemically Stable and Orally Active Inhibitors of the MDM2-p53 Interaction.
• Resolution: 1.73 Å
• Binding residue (original residue number in PDB): L54 I61 M62 F86 H96 I99 Y100
• Binding residue (residue number reindexed from 1): L36 I43 M44 F68 H78 I81 Y82
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=6.09,IC50=819nM

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:5lav, PDBe:5lav, PDBj:5lav
• PDBsum: 5lav
• PubMed: 27775892
• UniProt: Q00987|MDM2_HUMAN E3 ubiquitin-protein ligase Mdm2 (Gene Name=MDM2)