Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T00176 Target Info
Target Name Ubiquitin-protein ligase E3 Mdm2 (MDM2)
Synonyms RING-type E3 ubiquitin transferase Mdm2; P53-binding protein Mdm2; Oncoprotein Mdm2; MDM2 protein; Hdm2; E3 ubiquitin-protein ligase Mdm2; Double minute 2 protein
Target Type Clinical trial Target
Gene Name MDM2
Biochemical Class Acyltransferase
UniProt ID
MDM2_HUMAN
Ligand General Information  Top
Ligand Name nutlin-3A Ligand Info
Canonical SMILES CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl
InChI 1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)/t27-,28+/m0/s1
InChIKey BDUHCSBCVGXTJM-WUFINQPMSA-N
PubChem Compound ID 11433190
Drug Binding Sites of Target  Top
PDB ID: 5Z02      Crystal structure of HIS6-tagged Mdm2 with nutlin-3a
Method X-ray diffraction Resolution 1.35 Å Mutation No [1]
PDB Sequence
QETLVRPKPL
12
LLKLLKSVGA
22
QKDTYTMKEV
32
LFYLGQYIMT
42
KRLYDEKQQH
52

IVYCSNDLLG
62
DLFGVPSFSV
72
KEHRKIYTMI
82
YRNLVVVN
Residue
Distance (Å)
LEU33
3.247
PHE34
4.820
LEU36
4.069
GLY37
3.163
GLN38
4.521
ILE40
3.733
MET41
3.395
TYR46
4.457
GLN51
3.438
Residue
Distance (Å)
HIS52
3.341
VAL54
4.144
PHE65
3.685
PHE70
4.203
VAL72
3.404
HIS75
3.561
ILE78
3.755
TYR79
3.412
PDB ID: 4HG7      Crystal Structure of an MDM2/Nutlin-3a complex
Method X-ray diffraction Resolution 1.60 Å Mutation Yes [2]
PDB Sequence
QIPASEQETL
27
VRPKPLLLKL
37
LKSVGAQKDT
47
YTMKEVLFYL
57
GQYIMTKRLY
67

DAAQQHIVYC
77
SNDLLGDLFG
87
VPSFSVKEHR
97
KIYTMIYRNL
107
V
Residue
Distance (Å)
LEU54
3.686
LEU57
4.228
GLY58
3.622
GLN59
4.753
ILE61
3.550
MET62
3.445
TYR67
4.168
GLN72
3.205
HIS73
3.512
Residue
Distance (Å)
VAL75
3.721
PHE86
4.974
PHE91
4.043
VAL93
3.554
LYS94
4.807
HIS96
3.388
ILE99
3.859
TYR100
3.708
PDB ID: 5C5A      Crystal Structure of HDM2 in complex with Nutlin-3a
Method X-ray diffraction Resolution 1.15 Å Mutation No [3]
PDB Sequence
PASEQETLVR
29
PKPLLLKLLK
39
SVGAQKDTYT
49
MKEVLFYLGQ
59
YIMTKRLYDE
69

KQQHIVYCSN
79
DLLGDLFGVP
89
SFSVKEHRKI
99
YTMIYRNLVV
109
VN
Residue
Distance (Å)
VAL53
4.769
LEU54
2.704
PHE55
3.955
LEU57
2.886
GLY58
2.444
GLN59
2.042
ILE61
2.461
MET62
2.702
TYR67
2.700
GLN72
2.501
HIS73
2.244
ILE74
4.745
Residue
Distance (Å)
VAL75
2.864
LEU82
4.645
PHE86
3.511
PHE91
2.795
VAL93
2.341
LYS94
4.910
GLU95
4.643
HIS96
2.926
ILE99
2.205
TYR100
2.910
ILE103
3.629
PDB ID: 5ZXF      The 1.25A Crystal structure of His6-tagged Mdm2 in complex with nutlin-3a
Method X-ray diffraction Resolution 1.25 Å Mutation No [4]
PDB Sequence
QETLVRPKPL
12
LLKLLKSVGA
22
QKDTYTMKEV
32
LFYLGQYIMT
42
KRLYDEKQQH
52

IVYCSNDLLG
62
DLFGVPSFSV
72
KEHRKIYTMI
82
YRNLVVV
Click to Show 3D Structure of This Binding Site
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Residue
Distance (Å)
LEU33
3.186
PHE34
4.763
LEU36
4.092
GLY37
3.148
GLN38
4.427
ILE40
3.752
MET41
3.298
TYR46
4.404
GLN51
3.448
Residue
Distance (Å)
HIS52
3.427
VAL54
4.099
PHE65
3.612
PHE70
4.219
VAL72
3.377
HIS75
3.659
ILE78
3.830
TYR79
3.309
References  Top
REF 1 Crystal structure of HIS6-tagged Mdm2 with nutlin-3a
REF 2 The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant. Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1358-66.
REF 3 NMR Molecular Replacement, NMR2
REF 4 The 1.25A Crystal structure of His6-tagged Mdm2 in complex with nutlin-3a

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