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 T02702 Target Info
Target Name Bacterial Dihydrofolate reductase (Bact DHFR)
Synonyms Bact Dihydrofolate reductase
Target Type Clinical trial Target
Gene Name Bact DHFR
UniProt ID
DYR_ECOLI
Ligand General Information  Top
Ligand Name Deuterium Oxide Ligand Info
Canonical SMILES O
InChI 1S/H2O/h1H2/i/hD2
InChIKey XLYOFNOQVPJJNP-ZSJDYOACSA-N
PubChem Compound ID 24602
Drug Binding Sites of Target  Top
PDB ID: 4PDJ      Neutron crystal Structure of E.coli Dihydrofolate Reductase complexed with folate and NADP+
Method X-ray diffraction Resolution 1.60 Å Mutation No [1]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWNLPADLAW
30
FKRNTLNKPV
40
IMGRHTWESI
50

GRPLPGRKNI
60
ILSSQPGTDD
70
RVTWVKSVDE
80
AIAACGDVPE
90
IMVIGGGRVY
100

EQFLPKAQKL
110
YLTHIDAEVE
120
GDTHFPDYEP
130
DDWESVFSEF
140
HDADAQNSHS
150

YCFEILERR
Residue
Distance (Å)
MET1
1.961
ILE2
1.889
SER3
4.776
ILE5
2.429
ALA6
2.660
ALA7
3.616
LEU8
3.078
ALA9
2.388
VAL10
2.173
ASP11
1.951
ARG12
1.979
VAL13
2.357
ILE14
4.816
GLY15
3.931
MET16
2.817
GLU17
2.626
ASN18
1.788
ALA19
2.854
MET20
1.870
PRO21
4.799
TRP22
1.828
ASN23
1.795
LEU24
1.751
PRO25
2.042
ALA26
2.108
ASP27
1.663
LEU28
2.512
ALA29
2.323
TRP30
1.993
LYS32
2.090
ARG33
1.647
ASN34
1.966
THR35
3.575
LEU36
2.083
ASN37
2.637
LYS38
1.886
PRO39
2.519
ARG44
2.566
HIS45
2.706
THR46
3.473
TRP47
1.876
GLU48
1.931
SER49
1.853
ILE50
3.122
GLY51
2.147
ARG52
2.721
PRO53
2.508
LEU54
2.770
PRO55
2.611
GLY56
1.956
ARG57
2.516
LYS58
2.550
ASN59
1.828
ILE61
4.298
LEU62
4.421
SER63
2.328
SER64
2.847
GLN65
2.020
PRO66
2.056
GLY67
1.812
THR68
2.247
ASP69
1.881
ASP70
1.901
ARG71
1.879
VAL72
2.096
THR73
1.906
TRP74
1.989
VAL75
2.318
LYS76
2.303
SER77
1.775
VAL78
2.772
ASP79
2.008
Residue
Distance (Å)
GLU80
1.928
ILE82
1.800
ALA83
2.690
ALA84
4.874
CYS85
2.597
GLY86
2.058
ASP87
2.953
VAL88
1.970
PRO89
2.400
GLU90
2.037
ILE91
2.789
MET92
4.657
GLY97
2.999
ARG98
1.717
TYR100
4.031
GLU101
2.120
GLN102
2.026
PHE103
4.132
LEU104
2.527
PRO105
2.200
LYS106
2.353
ALA107
3.078
GLN108
1.747
LYS109
1.847
TYR111
2.084
LEU112
2.827
THR113
2.158
HIS114
1.658
ILE115
2.356
ASP116
1.549
ALA117
3.824
GLU118
2.297
VAL119
1.785
GLU120
1.979
GLY121
4.790
ASP122
1.984
THR123
2.318
HIS124
1.949
PHE125
2.974
PRO126
2.304
ASP127
4.830
TYR128
2.239
GLU129
1.758
PRO130
2.053
ASP131
2.031
ASP132
2.794
TRP133
2.071
GLU134
2.746
SER135
1.873
VAL136
3.112
SER138
1.741
GLU139
3.039
PHE140
1.984
HIS141
1.742
ASP142
1.954
ALA143
1.887
ASP144
2.304
ALA145
4.040
GLN146
2.140
ASN147
2.732
SER148
2.040
HIS149
2.420
SER150
1.926
TYR151
1.902
CYS152
2.806
PHE153
2.951
GLU154
2.005
LEU156
2.904
GLU157
1.579
ARG158
2.218
ARG159
2.233
PDB ID: 7D6G      Neutron crystal Structure of E.coli Dihydrofolate Reductase complexed with folate and NADP+ at pH4.5
Method X-ray diffraction Resolution 1.65 Å Mutation No [2]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWNLPADLAW
30
FKRNTLNKPV
40
IMGRHTWESI
50

GRPLPGRKNI
60
ILSSQPGTDD
70
RVTWVKSVDE
80
AIAACGDVPE
90
IMVIGGGRVY
100

EQFLPKAQKL
110
YLTHIDAEVE
120
GDTHFPDYEP
130
DDWESVFSEF
140
HDADAQNSHS
150

YCFEILERR
Residue
Distance (Å)
MET1
2.551
ILE2
2.063
SER3
4.775
ILE5
2.562
ALA6
2.560
ALA7
3.681
LEU8
2.652
ALA9
2.620
VAL10
1.976
ASP11
1.854
ARG12
2.306
VAL13
2.547
ILE14
4.261
GLY15
3.802
MET16
3.324
GLU17
2.165
ASN18
1.856
ALA19
2.611
MET20
1.978
PRO21
4.811
TRP22
1.946
ASN23
1.910
LEU24
1.953
PRO25
1.983
ALA26
2.298
ASP27
1.887
LEU28
2.703
ALA29
2.280
TRP30
2.107
LYS32
2.982
ARG33
2.190
ASN34
1.976
THR35
3.420
LEU36
2.024
ASN37
2.241
LYS38
1.942
PRO39
3.063
ARG44
2.521
HIS45
2.634
THR46
3.821
TRP47
2.115
GLU48
2.286
SER49
2.536
ILE50
2.851
GLY51
2.033
ARG52
2.549
PRO53
2.107
LEU54
2.599
PRO55
2.728
GLY56
2.004
ARG57
2.621
LYS58
2.380
ASN59
2.103
ILE61
4.718
LEU62
4.718
SER63
2.091
SER64
2.709
GLN65
1.987
PRO66
2.194
GLY67
1.819
THR68
2.156
ASP69
1.974
ASP70
1.699
ARG71
1.746
VAL72
2.054
THR73
1.687
TRP74
2.133
VAL75
2.846
LYS76
2.036
SER77
1.768
VAL78
3.980
ASP79
2.150
Residue
Distance (Å)
GLU80
2.093
ILE82
1.922
ALA83
2.903
ALA84
4.850
CYS85
3.004
GLY86
2.178
ASP87
3.723
VAL88
1.816
PRO89
2.471
GLU90
2.057
ILE91
2.340
MET92
4.834
GLY97
2.761
ARG98
2.418
TYR100
4.330
GLU101
2.101
GLN102
2.086
PHE103
4.122
LEU104
3.119
PRO105
2.485
LYS106
2.008
ALA107
3.317
GLN108
2.136
LYS109
2.111
TYR111
2.279
LEU112
2.747
THR113
2.110
HIS114
1.859
ILE115
2.025
ASP116
2.495
ALA117
3.778
GLU118
2.899
VAL119
1.956
GLU120
2.028
GLY121
3.532
ASP122
1.988
THR123
2.560
HIS124
1.862
PHE125
3.402
PRO126
2.717
ASP127
2.652
TYR128
2.095
GLU129
1.697
PRO130
2.942
ASP131
1.905
ASP132
2.417
TRP133
2.215
GLU134
2.748
SER135
2.121
VAL136
3.387
SER138
1.811
GLU139
2.499
PHE140
2.059
HIS141
1.705
ASP142
1.936
ALA143
2.109
ASP144
1.711
ALA145
4.350
GLN146
1.982
ASN147
2.588
SER148
1.817
HIS149
2.358
SER150
1.923
TYR151
2.033
CYS152
3.264
PHE153
2.830
GLU154
1.733
LEU156
3.005
GLU157
2.165
ARG158
1.904
ARG159
1.843
PDB ID: 2INQ      Neutron Crystal Structure of Escherichia coli Dihydrofolate Reductase Bound to the Anti-cancer drug, Methotrexate
Method Neutron diffraction Resolution 2.20 Å Mutation Yes [3]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWNLPADLAW
30
FKRNTLDKPV
40
IMGRHTWESI
50

GRPLPGRKNI
60
ILSSQPGTDD
70
RVTWVKSVDE
80
AIAACGDVPE
90
IMVIGGGRVY
100

EQFLPKAQKL
110
YLTHIDAEVE
120
GDTHFPDYEP
130
DDWESVFSEF
140
HDADAQNSHS
150

YCFEILERR
Residue
Distance (Å)
MET1
1.984
ILE2
3.083
ALA6
3.419
ALA7
4.931
ALA9
4.903
VAL10
1.535
ASP11
2.416
ARG12
4.645
ILE14
1.956
GLY15
2.621
MET16
3.645
GLU17
4.827
ASN23
2.566
PRO25
4.648
ALA26
2.101
ASP27
4.125
ALA29
3.456
TRP30
3.635
LYS32
4.827
ARG33
2.522
ASN34
3.608
ASP37
3.306
LYS38
3.736
PRO39
4.432
ARG44
4.188
HIS45
4.077
THR46
2.752
GLU48
1.909
SER49
4.468
GLY51
3.654
ARG52
4.354
PRO53
2.255
LEU54
3.903
PRO55
3.227
GLY56
2.234
ARG57
2.152
LYS58
2.658
ASN59
2.314
SER63
4.106
GLN65
2.258
PRO66
1.989
THR68
4.773
ASP70
4.728
ARG71
2.801
VAL72
3.794
THR73
4.041
TRP74
3.535
VAL75
3.138
LYS76
3.631
SER77
3.913
VAL78
2.677
ASP79
2.105
GLU80
1.966
ALA81
4.899
ILE82
4.026
ALA83
4.204
ALA84
3.246
Residue
Distance (Å)
VAL88
3.271
PRO89
1.921
GLU90
2.853
ILE91
3.288
ILE94
3.444
GLY95
2.773
GLY96
1.383
GLY97
3.460
ARG98
2.316
VAL99
4.720
TYR100
1.983
GLU101
2.274
GLN102
2.180
PHE103
4.133
LEU104
3.139
PRO105
4.221
LYS106
3.740
ALA107
4.389
GLN108
3.123
LEU112
2.544
THR113
1.976
HIS114
1.952
ASP116
4.824
ALA117
4.683
GLU118
3.420
GLU120
3.222
THR123
3.990
PHE125
4.916
PRO126
2.080
ASP127
4.161
TYR128
3.270
PRO130
4.678
ASP131
4.511
GLU134
4.056
SER135
4.016
PHE137
4.728
SER138
4.950
GLU139
2.604
PHE140
4.031
HIS141
2.135
ASP142
2.874
ALA143
4.148
ASP144
2.600
ALA145
3.966
GLN146
2.927
ASN147
2.169
SER148
2.787
HIS149
2.346
SER150
3.653
TYR151
2.545
CYS152
2.069
PHE153
2.067
GLU154
1.989
LEU156
3.465
ARG158
3.739
ARG159
2.877
References  Top
REF 1 Toward resolving the catalytic mechanism of dihydrofolate reductase using neutron and ultrahigh-resolution X-ray crystallography. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18225-30.
REF 2 Capturing the Catalytic Proton of Dihydrofolate Reductase: Implications for General Acid-Base Catalysis. doi:10.1021/acscatal.1c00417.
REF 3 Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18493-8.

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