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 T00442 Target Info
Target Name HUMAN catechol-O-methyl-transferase (COMT)
Synonyms S-COMT; MB-COMT; Catechol-O-methyltransferase; COMT
Gene Name COMT
Biochemical Class Methyltransferase
UniProt ID
COMT_HUMAN
Ligand General Information  Top
Ligand Name Ademetionine Ligand Info
Canonical SMILES C[S+](CCC(C(=O)[O-])N)CC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)O
InChI 1S/C15H22N6O5S/c1-27(3-2-7(16)15(24)25)4-8-10(22)11(23)14(26-8)21-6-20-9-12(17)18-5-19-13(9)21/h5-8,10-11,14,22-23H,2-4,16H2,1H3,(H2-,17,18,19,24,25)/t7-,8+,10+,11+,14+,27?/m0/s1
InChIKey MEFKEPWMEQBLKI-AIRLBKTGSA-N
PubChem Compound ID 34755
Drug Binding Sites of Target  Top
PDB ID: 6I3C      Crystal structure of Human soluble catechol O-methyltransferase in complex with 3,5-dinitrocatechol and S-adensoyl-L-methionine
Method X-ray diffraction Resolution 1.34 Å Mutation No [1]
PDB Sequence
GDTKEQRILN
11
HVLQHAEPGN
21
AQSVLEAIDT
31
YCEQKEWAMN
41
VGDKKGKIVD
51

AVIQEHQPSV
61
LLELGAYCGY
71
SAVRMARLLS
81
PGARLITIEI
91
NPDCAAITQR
101

MVDFAGVKDK
111
VTLVVGASQD
121
IIPQLKKKYD
131
VDTLDMVFLD
141
HWKDRYLPDT
151

LLLEECGLLR
161
KGTVLLADNV
171
ICPGAPDFLA
181
HVRGSSCFEC
191
THYQSFLEYR
201

EVVDGLEKAI
211
YKGP
Residue
Distance (Å)
MET40
3.342
ASN41
3.742
VAL42
2.866
GLU64
3.983
GLY66
2.942
ALA67
3.599
TYR68
3.357
GLY70
4.630
TYR71
3.386
SER72
2.795
ILE89
3.711
GLU90
2.765
ILE91
3.271
Residue
Distance (Å)
ASN92
4.064
CYS95
4.241
GLY117
3.739
ALA118
3.702
SER119
2.926
GLN120
3.336
PHE139
3.825
ASP141
2.717
HIS142
3.536
TRP143
3.491
LYS144
4.641
ARG146
3.921
PDB ID: 5LSA      human catechol O-methyltransferase in complex with SAM and DNC at 1.50A
Method X-ray diffraction Resolution 1.50 Å Mutation No [2]
PDB Sequence
DTKEQRILNH
62
VLQHAEPGNA
72
QSVLEAIDTY
82
CEQKEWAMNV
92
GDKKGKIVDA
102

VIQEHQPSVL
112
LELGAYCGYS
122
AVRMARLLSP
132
GARLITIEIN
142
PDCAAITQRM
152

VDFAGVKDKV
162
TLVVGASQDI
172
IPQLKKKYDV
182
DTLDMVFLDH
192
WKDRYLPDTL
202

LLEECGLLRK
212
GTVLLADNVI
222
CPGAPDFLAH
232
VRGSSCFECT
242
HYQSFLEYRE
252

VVDGLEKAIY
262
KGPG
Residue
Distance (Å)
MET90
3.426
ASN91
3.685
VAL92
2.814
GLU114
3.967
LEU115
4.998
GLY116
2.924
ALA117
3.556
TYR118
3.316
GLY120
4.536
TYR121
3.239
SER122
2.834
ILE139
3.665
GLU140
2.712
Residue
Distance (Å)
ILE141
3.190
ASN142
4.025
CYS145
4.274
GLY167
3.658
ALA168
3.656
SER169
2.883
GLN170
3.289
PHE189
3.791
ASP191
2.715
HIS192
3.474
TRP193
3.441
LYS194
4.462
ARG196
3.898
PDB ID: 4XUC      Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd18 (1-(biphenyl-3-yl)-3-hydroxypyridin-4(1H)-one)
Method X-ray diffraction Resolution 1.80 Å Mutation Yes [3]
PDB Sequence
NLLAGDTKEQ
57
RILNHVLQHA
67
EPGNAQSVLE
77
AIDTYCEQKE
87
WAMNVGDKKG
97

KIVDAVIQEH
107
QPSVLLELGA
117
YCGYSAVRMA
127
RLLSPGARLI
137
TIEINPDCAA
147

ITQRMVDFAG
157
VKDKVTLVVG
167
ASQDIIPQLK
177
KKYDVDTLDM
187
VFLDHWKDRY
197

LPDTLLLEEC
207
GLLRKGTVLL
217
ADNVICPGAP
227
DFLAHVRGSS
237
CFECTHYQSF
247

LEYREVVDGL
257
EKAIYKGP
Residue
Distance (Å)
MET90
3.327
ASN91
3.636
VAL92
2.775
GLU114
3.804
GLY116
2.784
ALA117
3.532
TYR118
3.392
GLY120
4.589
TYR121
3.299
SER122
2.785
ILE139
3.823
GLU140
2.645
ILE141
3.245
Residue
Distance (Å)
ASN142
4.041
CYS145
4.413
GLY167
3.507
ALA168
3.677
SER169
2.870
GLN170
3.636
PHE189
3.916
ASP191
2.798
HIS192
3.641
TRP193
3.067
LYS194
4.446
ARG196
4.467
ASP200
4.678
PDB ID: 4XUD      Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd32 ([1-(biphenyl-3-yl)-5-hydroxy-4-oxo-1,4-dihydropyridin-3-yl]boronic acid)
Method X-ray diffraction Resolution 2.40 Å Mutation Yes [3]
PDB Sequence
NLLAGDTKEQ
57
RILNHVLQHA
67
EPGNAQSVLE
77
AIDTYCEQKE
87
WAMNVGDKKG
97

KIVDAVIQEH
107
QPSVLLELGA
117
YCGYSAVRMA
127
RLLSPGARLI
137
TIEINPDCAA
147

ITQRMVDFAG
157
VKDKVTLVVG
167
ASQDIIPQLK
177
KKYDVDTLDM
187
VFLDHWKDRY
197

LPDTLLLEEC
207
GLLRKGTVLL
217
ADNVICPGAP
227
DFLAHVRGSS
237
CFECTHYQSF
247

LEYREVVDGL
257
EKAIYKGP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SAM or .SAM2 or .SAM3 or :3SAM;style chemicals stick;color identity;select .A:90 or .A:91 or .A:92 or .A:114 or .A:116 or .A:117 or .A:118 or .A:120 or .A:121 or .A:122 or .A:139 or .A:140 or .A:141 or .A:142 or .A:145 or .A:167 or .A:168 or .A:169 or .A:170 or .A:189 or .A:191 or .A:192 or .A:193 or .A:194 or .A:196 or .A:200; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
MET90
3.270
ASN91
3.624
VAL92
2.811
GLU114
3.819
GLY116
2.951
ALA117
3.362
TYR118
3.557
GLY120
4.560
TYR121
3.291
SER122
2.876
ILE139
3.613
GLU140
2.704
ILE141
3.181
Residue
Distance (Å)
ASN142
4.167
CYS145
4.334
GLY167
3.547
ALA168
3.725
SER169
2.937
GLN170
3.618
PHE189
3.770
ASP191
2.773
HIS192
3.579
TRP193
3.087
LYS194
4.537
ARG196
4.749
ASP200
4.810
PDB ID: 3A7E      Crystal structure of human COMT complexed with SAM and 3,5-dinitrocatechol
Method X-ray diffraction Resolution 2.80 Å Mutation No [4]
PDB Sequence
DTKEQRILNH
12
VLQHAEPGNA
22
QSVLEAIDTY
32
CEQKEWAMNV
42
GDKKGKIVDA
52

VIQEHQPSVL
62
LELGAYCGYS
72
AVRMARLLSP
82
GARLITIEIN
92
PDCAAITQRM
102

VDFAGVKDKV
112
TLVVGASQDI
122
IPQLKKKYDV
132
DTLDMVFLDH
142
WKDRYLPDTL
152

LLEECGLLRK
162
GTVLLADNVI
172
CPGAPDFLAH
182
VRGSSCFECT
192
HYQSFLEYRE
202

VVDGLEKAIY
212
KG
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SAM or .SAM2 or .SAM3 or :3SAM;style chemicals stick;color identity;select .A:40 or .A:41 or .A:42 or .A:64 or .A:65 or .A:66 or .A:67 or .A:68 or .A:70 or .A:71 or .A:72 or .A:89 or .A:90 or .A:91 or .A:92 or .A:95 or .A:117 or .A:118 or .A:119 or .A:120 or .A:139 or .A:141 or .A:142 or .A:143 or .A:144 or .A:146 or .A:150 or .A:170; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
MET40
3.260
ASN41
3.742
VAL42
2.977
GLU64
3.558
LEU65
4.887
GLY66
2.823
ALA67
3.317
TYR68
3.578
GLY70
4.824
TYR71
3.479
SER72
2.886
ILE89
3.249
GLU90
2.492
ILE91
3.247
Residue
Distance (Å)
ASN92
3.864
CYS95
3.805
GLY117
3.626
ALA118
3.784
SER119
2.829
GLN120
3.388
PHE139
4.182
ASP141
3.049
HIS142
3.532
TRP143
3.332
LYS144
4.715
ARG146
3.482
ASP150
4.749
ASN170
4.925
PDB ID: 4XUE      Synthesis and evaluation of heterocyclic catechol mimics as inhibitors of catechol-O-methyltransferase (COMT): Structure with Cmpd27b
Method X-ray diffraction Resolution 2.30 Å Mutation No [3]
PDB Sequence
AGDTKEQRIL
60
NHVLQHAEPG
70
NAQSVLEAID
80
TYCEQKEWAM
90
NVGDKKGKIV
100

DAVIQEHQPS
110
VLLELGAYCG
120
YSAVRMARLL
130
SPGARLITIE
140
INPDCAAITQ
150

RMVDFAGVKD
160
KVTLVVGASQ
170
DIIPQLKKKY
180
DVDTLDMVFL
190
DHWKDRYLPD
200

TLLLEECGLL
210
RKGTVLLADN
220
VICPGAPDFL
230
AHVRGSSCFE
240
CTHYQSFLEY
250

REVVDGLEKA
260
IYKGP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SAM or .SAM2 or .SAM3 or :3SAM;style chemicals stick;color identity;select .B:90 or .B:91 or .B:92 or .B:114 or .B:115 or .B:116 or .B:117 or .B:118 or .B:120 or .B:121 or .B:122 or .B:139 or .B:140 or .B:141 or .B:142 or .B:145 or .B:167 or .B:168 or .B:169 or .B:170 or .B:189 or .B:191 or .B:192 or .B:193 or .B:194 or .B:196 or .B:200; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
MET90
3.211
ASN91
3.653
VAL92
2.785
GLU114
4.127
LEU115
4.961
GLY116
2.851
ALA117
3.665
TYR118
3.344
GLY120
4.562
TYR121
3.217
SER122
2.900
ILE139
3.586
GLU140
2.747
ILE141
3.263
Residue
Distance (Å)
ASN142
3.869
CYS145
4.107
GLY167
3.665
ALA168
3.677
SER169
2.907
GLN170
3.247
PHE189
4.011
ASP191
2.630
HIS192
3.574
TRP193
3.362
LYS194
4.653
ARG196
4.013
ASP200
4.968
PDB ID: 3BWY      Crystal Structure of Human 108M Catechol O-methyltransferase bound with S-adenosylmethionine and inhibitor dinitrocatechol
Method X-ray diffraction Resolution 1.30 Å Mutation No [5]
PDB Sequence
GDTKEQRILN
11
HVLQHAEPGN
21
AQSVLEAIDT
31
YCEQKEWAMN
41
VGDKKGKIVD
51

AVIQEHQPSV
61
LLELGAYCGY
71
SAVRMARLLS
81
PGARLITIEI
91
NPDCAAITQR
101

MVDFAGMKDK
111
VTLVVGASQD
121
IIPQLKKKYD
131
VDTLDMVFLD
141
HWKDRYLPDT
151

LLLEECGLLR
161
KGTVLLADNV
171
ICPGAPDFLA
181
HVRGSSCFEC
191
THYQSFLEYR
201

EVVDGLEKAI
211
YKGP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SAM or .SAM2 or .SAM3 or :3SAM;style chemicals stick;color identity;select .A:40 or .A:41 or .A:42 or .A:64 or .A:66 or .A:67 or .A:68 or .A:70 or .A:71 or .A:72 or .A:89 or .A:90 or .A:91 or .A:92 or .A:95 or .A:117 or .A:118 or .A:119 or .A:120 or .A:139 or .A:141 or .A:142 or .A:143 or .A:144 or .A:146 or .A:150; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
MET40
3.440
ASN41
3.721
VAL42
2.838
GLU64
3.935
GLY66
2.904
ALA67
3.582
TYR68
3.324
GLY70
4.543
TYR71
3.248
SER72
2.751
ILE89
3.692
GLU90
2.670
ILE91
3.221
Residue
Distance (Å)
ASN92
4.020
CYS95
4.187
GLY117
3.684
ALA118
3.581
SER119
2.876
GLN120
3.136
PHE139
3.836
ASP141
2.681
HIS142
3.585
TRP143
3.380
LYS144
4.457
ARG146
3.916
ASP150
4.988
PDB ID: 3BWM      Crystal Structure of Human Catechol O-Methyltransferase with bound SAM and DNC
Method X-ray diffraction Resolution 1.98 Å Mutation No [5]
PDB Sequence
GDTKEQRILN
11
HVLQHAEPGN
21
AQSVLEAIDT
31
YCEQKEWAMN
41
VGDKKGKIVD
51

AVIQEHQPSV
61
LLELGAYCGY
71
SAVRMARLLS
81
PGARLITIEI
91
NPDCAAITQR
101

MVDFAGVKDK
111
VTLVVGASQD
121
IIPQLKKKYD
131
VDTLDMVFLD
141
HWKDRYLPDT
151

LLLEECGLLR
161
KGTVLLADNV
171
ICPGAPDFLA
181
HVRGSSCFEC
191
THYQSFLEYR
201

EVVDGLEKAI
211
YKGP
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SAM or .SAM2 or .SAM3 or :3SAM;style chemicals stick;color identity;select .A:40 or .A:41 or .A:42 or .A:64 or .A:66 or .A:67 or .A:68 or .A:70 or .A:71 or .A:72 or .A:89 or .A:90 or .A:91 or .A:92 or .A:95 or .A:117 or .A:118 or .A:119 or .A:120 or .A:139 or .A:141 or .A:142 or .A:143 or .A:144 or .A:146; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
MET40
3.350
ASN41
3.665
VAL42
2.810
GLU64
4.045
GLY66
2.848
ALA67
3.634
TYR68
3.325
GLY70
4.575
TYR71
3.287
SER72
2.905
ILE89
3.840
GLU90
2.718
ILE91
3.252
Residue
Distance (Å)
ASN92
3.999
CYS95
4.280
GLY117
3.609
ALA118
3.526
SER119
2.873
GLN120
3.155
PHE139
3.912
ASP141
2.866
HIS142
3.492
TRP143
3.462
LYS144
4.613
ARG146
4.040
References  Top
REF 1 Equatorial Active Site Compaction and Electrostatic Reorganization in Catechol-O-methyltransferase. ACS Catal. 2019 May 3;9(5):4394-4401.
REF 2 human catechol O-methyltransferase in complex with SAM and DNC at 1.50A
REF 3 Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT). ACS Med Chem Lett. 2015 Jan 26;6(3):318-23.
REF 4 Hit to Lead: Comprehensive Strategy of de novo Scaffold Generation by FBDD. Part 1: In silico Fragments Linking and Verification of Spatial Proximity using Inter Ligand NOE Approachs
REF 5 Crystal structures of human 108V and 108M catechol O-methyltransferase. J Mol Biol. 2008 Jun 27;380(1):120-30.

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