Structure of PDB 4lwu Chain A Binding Site BS01

Receptor Information
>4lwu Chain A (length=85) Species: 8355 (Xenopus laevis) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EKLVQPTPLLLSLLKSAGAQKETFTMKEVLYHLGQYIMAKQLYDEKQQHI
VHCSNDPLGELFGVQEFSVKEHRRIYAMISRNLVS
Ligand information
Ligand ID20U
InChIInChI=1S/C30H29Cl2FN4O3/c1-29(2,3)14-22-30(19-12-9-16(31)13-21(19)36-28(30)40)23(18-5-4-6-20(32)24(18)33)25(37-22)27(39)35-17-10-7-15(8-11-17)26(34)38/h4-13,22-23,25,37H,14H2,1-3H3,(H2,34,38)(H,35,39)(H,36,40)/t22-,23-,25+,30+/m0/s1
InChIKeyKALNCVZAFDQICX-AMKZZFPWSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01O=C(N)c1ccc(cc1)NC(=O)C5NC(C2(c3c(NC2=O)cc(Cl)cc3)C5c4cccc(Cl)c4F)CC(C)(C)C
OpenEye OEToolkits 1.7.6CC(C)(C)CC1C2(c3ccc(cc3NC2=O)Cl)C(C(N1)C(=O)Nc4ccc(cc4)C(=O)N)c5cccc(c5F)Cl
CACTVS 3.385CC(C)(C)C[CH]1N[CH]([CH](c2cccc(Cl)c2F)[C]13C(=O)Nc4cc(Cl)ccc34)C(=O)Nc5ccc(cc5)C(N)=O
OpenEye OEToolkits 1.7.6CC(C)(C)C[C@H]1[C@]2(c3ccc(cc3NC2=O)Cl)[C@H]([C@@H](N1)C(=O)Nc4ccc(cc4)C(=O)N)c5cccc(c5F)Cl
CACTVS 3.385CC(C)(C)C[C@@H]1N[C@H]([C@H](c2cccc(Cl)c2F)[C@]13C(=O)Nc4cc(Cl)ccc34)C(=O)Nc5ccc(cc5)C(N)=O
FormulaC30 H29 Cl2 F N4 O3
Name(2'S,3R,4'S,5'R)-N-(4-carbamoylphenyl)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxamide
ChEMBLCHEMBL3310185
DrugBank
ZINCZINC000072316544
PDB chain4lwu Chain A Residue 201 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4lwu Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.
Resolution1.14 Å
Binding residue
(original residue number in PDB)		L50 L53 I57 M58 H69 F82 V89 K90 H92 I95 Y96
Binding residue
(residue number reindexed from 1)		L30 L33 I37 M38 H49 F62 V69 K70 H72 I75 Y76
Annotation score1
Binding affinityMOAD: ic50=0.005uM
PDBbind-CN: -logKd/Ki=8.30,IC50=0.005uM
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

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Biological Process
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Cellular Component
External links
PDB RCSB:4lwu, PDBe:4lwu, PDBj:4lwu
PDBsum4lwu
PubMed24997575
UniProtP56273|MDM2_XENLA E3 ubiquitin-protein ligase Mdm2 (Gene Name=mdm2)

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