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 T03500 Target Info
Target Name Matrix metalloproteinase-12 (MMP-12)
Synonyms Macrophage metalloelastase; Macrophage elastase; MME; ME; HME
Target Type Clinical trial Target
Gene Name MMP12
Biochemical Class Peptidase
UniProt ID
MMP12_HUMAN
Ligand General Information  Top
Ligand Name N-[(2r)-2-{[3-(3'-Chlorobiphenyl-4-Yl)-1,2-Oxazol-5-Yl]methyl}-4-(Hydroxyamino)-4-Oxobutanoyl]-L-Alpha-Glutamyl-L-Alpha-Glutamine Ligand Info
Canonical SMILES C1=CC(=CC(=C1)Cl)C2=CC=C(C=C2)C3=NOC(=C3)CC(CC(=O)NO)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)O)C(=O)N
InChI 1S/C30H32ClN5O10/c31-20-3-1-2-18(12-20)16-4-6-17(7-5-16)24-15-21(46-36-24)13-19(14-25(37)35-45)29(43)34-23(9-11-27(40)41)30(44)33-22(28(32)42)8-10-26(38)39/h1-7,12,15,19,22-23,45H,8-11,13-14H2,(H2,32,42)(H,33,44)(H,34,43)(H,35,37)(H,38,39)(H,40,41)/t19-,22+,23+/m1/s1
InChIKey VBMQORMYXJZHKU-OIBXWCBGSA-N
PubChem Compound ID 121493953
Drug Binding Sites of Target  Top
PDB ID: 5D2B      Crystal structure of a mutated catalytic domain of Human MMP12 in complex with an hydroxamate analogue of RXP470
Method X-ray diffraction Resolution 1.20 Å Mutation Yes [1]
PDB Sequence
MGPVWRKHYI
114
TYRINNYTPD
124
MNREDVDYAI
134
RKAFQVWSNV
144
TPLKFSKINT
154

GMADILVVFA
164
RGAHGDDHAF
174
DGKGGILAHA
184
FGPGSGIGGD
194
AHFDEDEFWT
204

THSGGTNLFL
214
TAVHEIGHSL
224
GLGHSSDPKA
234
VMFPTYKYVD
244
INTFRLSADD
254

IRGIQSLYG
Residue
Distance (Å)
GLY178
3.265
GLY179
3.432
ILE180
3.407
LEU181
2.758
ALA182
3.027
HIS183
4.031
ALA184
4.576
GLU201
4.486
THR210
4.389
LEU214
4.005
THR215
3.257
HIS218
2.981
GLU219
2.784
HIS222
2.864
Residue
Distance (Å)
HIS228
2.804
PRO232
3.562
LYS233
3.452
ALA234
3.554
VAL235
3.311
MET236
4.981
PHE237
3.195
PRO238
3.148
THR239
3.174
TYR240
2.709
LYS241
3.401
VAL243
3.586
PHE248
3.243
ARG249
4.297
PDB ID: 5D3C      Crystal structure of a double mutant catalytic domain of Human MMP12 in complex with an hydroxamate analogue of RXP470
Method X-ray diffraction Resolution 1.31 Å Mutation Yes [1]
PDB Sequence
MGPVWRKHYI
114
TYRINNYTPD
124
MNREDVDYAI
134
RKAFQVWSNV
144
TPLKFSKINT
154

GMADILVVFA
164
RGAHGDDHAF
174
DGKGGILAHA
184
FGPGSGIGGD
194
AHFDEDEFWT
204

THSGGTNLFL
214
TAVHEIGHSL
224
GLGHSSDPKA
234
VMFPTYAYVD
244
INTFRLSADD
254

IRGIQSLYG
Residue
Distance (Å)
LYS177
4.956
GLY178
3.603
GLY179
2.989
ILE180
3.600
LEU181
2.795
ALA182
2.864
HIS183
3.941
ALA184
4.468
GLU201
4.209
THR210
4.303
LEU214
4.078
THR215
3.329
HIS218
3.235
GLU219
2.785
HIS222
3.041
Residue
Distance (Å)
HIS228
2.862
PRO232
3.196
LYS233
3.283
ALA234
3.533
VAL235
3.333
MET236
4.923
PHE237
3.287
PRO238
3.090
THR239
3.324
TYR240
2.922
ALA241
3.659
VAL243
3.771
PHE248
3.185
ARG249
4.018
References  Top
REF 1 Zinc-Metalloproteinase Inhibitors: Evaluation of the Complex Role Played by the Zinc-Binding Group on Potency and Selectivity. J Med Chem. 2017 Jan 12;60(1):403-414.

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