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 Methotrexate Ligand Info
Canonical SMILES CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
InChI 1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
InChIKey FBOZXECLQNJBKD-ZDUSSCGKSA-N
PubChem Compound ID 126941
Drug Binding Sites of Target  Top
PDB ID: 3DAU      Crystal structure of the ternary MTX NADPH complex of Escherichia coli dihydrofolate reductase
Method X-ray diffraction Resolution 1.50 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)
ILE5
2.818
ALA6
3.422
ALA7
3.773
MET20
2.890
PRO25
3.409
ASP27
2.659
LEU28
3.449
ALA29
3.530
TRP30
4.141
PHE31
3.416
LYS32
3.324
THR35
4.875
Residue
Distance (Å)
THR46
4.132
SER49
3.927
ILE50
3.543
ARG52
2.941
LEU54
3.665
PRO55
4.211
ARG57
2.754
VAL93
4.982
ILE94
2.915
GLY95
4.713
TYR100
3.235
THR113
3.528
PDB ID: 4DFR      CRYSTAL STRUCTURES OF ESCHERICHIA COLI AND LACTOBACILLUS CASEI DIHYDROFOLATE REDUCTASE REFINED AT 1.7 ANGSTROMS RESOLUTION. I. GENERAL FEATURES AND BINDING OF METHOTREXATE
Method X-ray diffraction Resolution 1.70 Å Mutation No [2]
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

YCFKILERR
Residue
Distance (Å)
ILE5
2.727
ALA6
3.517
ALA7
3.776
ASP27
2.481
LEU28
3.749
TRP30
4.118
PHE31
3.295
LYS32
3.583
THR35
4.843
THR46
3.956
Residue
Distance (Å)
SER49
3.816
ILE50
3.747
ARG52
2.884
LEU54
3.739
PRO55
4.441
ARG57
2.572
ILE94
2.841
GLY95
4.744
TYR100
3.446
THR113
3.685
PDB ID: 1DHJ      LONG-RANGE STRUCTURAL EFFECTS IN A SECOND-SITE REVERTANT OF A MUTANT DIHYDROFOLATE REDUCTASE
Method X-ray diffraction Resolution 1.80 Å Mutation No [3]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWNLPASLAW
30
FKRNTLDKPV
40
IMGRHTWESI
50

GRPLPGRKNI
60
ILSSQPGTDD
70
RVTWVKSVDE
80
AIAACGDVPE
90
IMVIGGGRVY
100

EQFLPKAQKL
110
YLTHIDAEVE
120
GDTHFPDYEP
130
DDWESVSSEF
140
HDADAQNSHS
150

YCFEILERR
Residue
Distance (Å)
ILE5
2.730
ALA6
3.380
ALA7
3.663
SER27
4.438
LEU28
3.683
TRP30
4.444
PHE31
3.480
LYS32
3.624
THR46
4.111
SER49
3.697
Residue
Distance (Å)
ILE50
3.624
ARG52
2.659
LEU54
3.722
PRO55
4.403
ARG57
2.702
ILE94
2.844
GLY95
4.831
TYR100
3.202
THR113
3.425
PDB ID: 1RA3      DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (OXIDIZED FORM)
Method X-ray diffraction Resolution 1.80 Å Mutation No [4]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.784
ALA6
3.445
ALA7
3.770
ASP27
2.693
LEU28
3.577
ALA29
4.520
TRP30
4.242
PHE31
3.343
LYS32
2.978
THR35
4.652
THR46
4.362
Residue
Distance (Å)
SER49
4.376
ILE50
3.672
ARG52
3.104
LEU54
3.997
PRO55
4.572
ARG57
2.604
ILE94
2.950
GLY95
4.934
TYR100
3.332
THR113
3.612
PDB ID: 1DHI      LONG-RANGE STRUCTURAL EFFECTS IN A SECOND-SITE REVERTANT OF A MUTANT DIHYDROFOLATE REDUCTASE
Method X-ray diffraction Resolution 1.90 Å Mutation No [3]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWNLPASLAW
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.862
ALA6
3.510
ALA7
3.762
SER27
4.005
LEU28
3.719
TRP30
4.374
PHE31
3.541
LYS32
3.526
THR46
4.245
SER49
3.609
Residue
Distance (Å)
ILE50
3.563
ARG52
3.068
LEU54
3.899
PRO55
4.482
ARG57
2.634
ILE94
2.901
GLY95
4.850
TYR100
3.418
THR113
3.498
PDB ID: 1DRA      CRYSTAL STRUCTURE OF UNLIGANDED ESCHERICHIA COLI DIHYDROFOLATE REDUCTASE. LIGAND-INDUCED CONFORMATIONAL CHANGES AND COOPERATIVITY IN BINDING
Method X-ray diffraction Resolution 1.90 Å Mutation No [5]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWNLPAELAW
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.837
ALA6
3.452
ALA7
3.749
GLU27
2.474
LEU28
3.722
TRP30
4.248
PHE31
3.411
LYS32
3.533
THR35
4.952
THR46
4.246
Residue
Distance (Å)
SER49
3.663
ILE50
3.586
ARG52
2.920
LEU54
3.899
PRO55
4.507
ARG57
2.709
ILE94
2.946
GLY95
4.843
TYR100
3.486
THR113
3.684
PDB ID: 2DRC      INVESTIGATION OF THE FUNCTIONAL ROLE OF TRYPTOPHAN-22 IN ESCHERICHIA COLI DIHYDROFOLATE REDUCTASE BY SITE-DIRECTED MUTAGENESIS
Method X-ray diffraction Resolution 1.90 Å Mutation No [6]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PFNLPADLAW
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.775
ALA6
3.506
ALA7
3.785
ASP27
2.670
LEU28
3.859
TRP30
4.190
PHE31
3.401
LYS32
3.578
THR35
4.916
THR46
4.052
Residue
Distance (Å)
SER49
3.606
ILE50
3.621
ARG52
2.885
LEU54
3.871
PRO55
4.393
ARG57
2.624
ILE94
2.814
GLY95
4.762
TYR100
3.355
THR113
3.637
PDB ID: 3DRC      INVESTIGATION OF THE FUNCTIONAL ROLE OF TRYPTOPHAN-22 IN ESCHERICHIA COLI DIHYDROFOLATE REDUCTASE BY SITE-DIRECTED MUTAGENESIS
Method X-ray diffraction Resolution 1.90 Å Mutation No [6]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.803
ALA6
3.494
ALA7
3.768
ASP27
2.698
LEU28
3.767
TRP30
4.259
PHE31
3.339
LYS32
3.513
THR35
4.886
THR46
4.196
Residue
Distance (Å)
SER49
3.670
ILE50
3.663
ARG52
3.006
LEU54
3.928
PRO55
4.519
ARG57
2.686
ILE94
2.915
GLY95
4.902
TYR100
3.434
THR113
3.580
PDB ID: 1DRB      CRYSTAL STRUCTURE OF UNLIGANDED ESCHERICHIA COLI DIHYDROFOLATE REDUCTASE. LIGAND-INDUCED CONFORMATIONAL CHANGES AND COOPERATIVITY IN BINDING
Method X-ray diffraction Resolution 1.96 Å Mutation No [5]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWNLPACLAW
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:28 or .A:30 or .A:31 or .A:32 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.807
ALA6
3.260
ALA7
3.676
LEU28
3.897
TRP30
4.482
PHE31
3.558
LYS32
3.533
THR46
4.313
SER49
3.732
Residue
Distance (Å)
ILE50
3.561
ARG52
2.945
LEU54
3.967
PRO55
4.459
ARG57
2.692
ILE94
2.886
GLY95
4.757
TYR100
3.340
THR113
3.468
PDB ID: 1RG7      DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE
Method X-ray diffraction Resolution 2.00 Å Mutation No [4]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:17 or .A:18 or .A:19 or .A:23 or .A:27 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.770
ALA6
3.425
ALA7
3.726
GLU17
4.107
ASN18
3.364
ALA19
3.378
ASN23
3.649
ASP27
2.640
LEU28
3.361
ALA29
4.488
TRP30
4.302
PHE31
3.390
LYS32
3.422
Residue
Distance (Å)
THR35
4.812
THR46
3.937
SER49
3.718
ILE50
3.391
ARG52
4.203
LEU54
3.758
PRO55
4.504
ARG57
2.556
ILE94
2.903
GLY95
4.813
TYR100
3.230
THR113
3.474
PDB ID: 1DDS      MOLECULE: DIHYDROFOLATE REDUCTASE (E.C.1.5.1.3) COMPLEXED WITH METHOTREXATE
Method X-ray diffraction Resolution 2.20 Å Mutation No [7]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.701
ALA6
3.547
ALA7
3.809
ASP27
2.883
LEU28
3.621
TRP30
4.297
PHE31
3.027
LYS32
3.670
THR35
4.362
THR46
3.894
Residue
Distance (Å)
SER49
4.155
ILE50
3.623
ARG52
3.292
LEU54
3.709
PRO55
4.659
ARG57
2.640
ILE94
2.600
GLY95
4.611
TYR100
3.308
THR113
3.659
PDB ID: 1RX3      DIHYDROFOLATE REDUCTASE (E.C.1.5.1.3) COMPLEXED WITH METHOTREXATE AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (REDUCED FORM)
Method X-ray diffraction Resolution 2.20 Å Mutation No [4]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:20 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:100 or .A:113; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.749
ALA6
3.281
ALA7
3.441
MET20
3.177
ASP27
2.321
LEU28
3.603
TRP30
4.381
PHE31
3.084
LYS32
3.228
THR35
4.653
Residue
Distance (Å)
THR46
4.769
SER49
3.964
ILE50
3.303
ARG52
3.265
LEU54
3.652
PRO55
4.531
ARG57
2.688
ILE94
3.073
TYR100
3.320
THR113
3.840
PDB ID: 1RB3      DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (OXIDIZED FORM)
Method X-ray diffraction Resolution 2.30 Å Mutation No [4]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.867
ALA6
3.520
ALA7
3.704
ASP27
2.484
LEU28
3.512
TRP30
4.167
PHE31
3.405
LYS32
3.474
THR46
4.271
SER49
4.356
Residue
Distance (Å)
ILE50
3.508
ARG52
4.009
LEU54
4.121
PRO55
4.231
ARG57
3.093
ILE94
2.972
GLY95
4.831
TYR100
3.479
THR113
3.575
PDB ID: 1RH3      DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (REDUCED FORM)
Method X-ray diffraction Resolution 2.40 Å Mutation No [4]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:20 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.713
ALA6
3.516
ALA7
3.943
MET20
3.378
ASP27
2.733
LEU28
3.388
TRP30
4.353
PHE31
3.254
LYS32
3.282
THR35
4.901
Residue
Distance (Å)
THR46
4.157
SER49
3.533
ILE50
3.907
ARG52
2.842
LEU54
3.994
ARG57
2.960
ILE94
2.880
GLY95
4.718
TYR100
3.331
THR113
4.088
PDB ID: 1DDR      MOLECULE: DIHYDROFOLATE REDUCTASE (E.C.1.5.1.3) COMPLEXED WITH METHOTREXATE AND UREA
Method X-ray diffraction Resolution 2.45 Å Mutation No [7]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:111 or .A:113; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.514
ALA6
3.229
ALA7
3.809
ASP27
2.823
LEU28
3.853
TRP30
4.003
PHE31
3.313
LYS32
3.530
THR35
4.095
THR46
3.657
SER49
3.834
Residue
Distance (Å)
ILE50
3.833
ARG52
2.820
LEU54
3.554
PRO55
4.523
ARG57
2.716
ILE94
2.701
GLY95
4.703
TYR100
3.517
TYR111
4.520
THR113
3.476
PDB ID: 1TDR      EXPRESSION, CHARACTERIZATION, AND CRYSTALLOGRAPHIC ANALYSIS OF TELLUROMETHIONYL DIHYDROFOLATE REDUCTASE
Method X-ray diffraction Resolution 2.50 Å Mutation No [8]
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

YCFKILERR
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:27 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:55 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.679
ALA6
3.839
ALA7
3.810
ASP27
2.660
LEU28
3.699
ALA29
4.924
TRP30
4.147
PHE31
3.241
LYS32
3.334
THR35
4.792
THR46
3.937
Residue
Distance (Å)
SER49
3.991
ILE50
3.770
ARG52
2.423
LEU54
3.459
PRO55
4.249
ARG57
2.595
ILE94
2.789
GLY95
4.810
TYR100
3.430
THR113
3.393
PDB ID: 1DRE      DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE AND NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (OXIDIZED FORM)
Method X-ray diffraction Resolution 2.60 Å Mutation No [4]
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
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .A:5 or .A:6 or .A:7 or .A:20 or .A:27 or .A:28 or .A:30 or .A:31 or .A:32 or .A:35 or .A:46 or .A:49 or .A:50 or .A:52 or .A:54 or .A:57 or .A:94 or .A:95 or .A:100 or .A:113; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.597
ALA6
3.396
ALA7
3.762
MET20
3.337
ASP27
2.786
LEU28
3.484
TRP30
4.335
PHE31
3.203
LYS32
3.108
THR35
4.799
Residue
Distance (Å)
THR46
4.091
SER49
3.358
ILE50
3.752
ARG52
2.794
LEU54
3.947
ARG57
2.913
ILE94
3.108
GLY95
4.780
TYR100
3.306
THR113
4.019
PDB ID: 4GH8      Crystal structure of a 'humanized' E. coli dihydrofolate reductase
Method X-ray diffraction Resolution 1.85 Å Mutation No [9]
PDB Sequence
MISLIAALAV
10
DRVIGMENAM
20
PWPPLPADLA
30
WFKRNTLNKP
40
VIMGRHTWES
50

IPEKNRPLPG
60
RKNIILSSQP
70
GTDDRVTWVK
80
SVDEAIAACG
90
DVPEIMVIGG
100

GRVYEQFLPK
110
AQKLYLTHID
120
AEVEGDTHFP
130
DYEPDDWESV
140
FSEFHDADAQ
150

NSHSYCFEIL
160
ER
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MTX or .MTX2 or .MTX3 or :3MTX;style chemicals stick;color identity;select .B:5 or .B:6 or .B:7 or .B:20 or .B:26 or .B:28 or .B:29 or .B:30 or .B:31 or .B:32 or .B:33 or .B:36 or .B:47 or .B:50 or .B:51 or .B:52 or .B:55 or .B:58 or .B:59 or .B:61 or .B:98 or .B:99 or .B:104 or .B:117; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE5
2.900
ALA6
3.460
ALA7
3.586
MET20
3.359
PRO26
4.548
ASP28
2.756
LEU29
3.276
ALA30
4.265
TRP31
4.227
PHE32
3.058
LYS33
3.577
THR36
4.957
Residue
Distance (Å)
THR47
4.521
SER50
3.605
ILE51
3.866
PRO52
3.774
ASN55
2.565
LEU58
4.091
PRO59
4.144
ARG61
2.854
ILE98
3.037
GLY99
4.939
TYR104
3.404
THR117
3.572
References  Top
REF 1 X-ray structure of the ternary MTX.NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design. J Struct Biol. 2009 May;166(2):162-71.
REF 2 Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. I. General features and binding of methotrexate. J Biol Chem. 1982 Nov 25;257(22):13650-62.
REF 3 Long-range structural effects in a second-site revertant of a mutant dihydrofolate reductase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11753-6.
REF 4 Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. Biochemistry. 1997 Jan 21;36(3):586-603.
REF 5 Crystal structure of unliganded Escherichia coli dihydrofolate reductase. Ligand-induced conformational changes and cooperativity in binding. Biochemistry. 1991 Feb 26;30(8):2227-39.
REF 6 Investigation of the functional role of tryptophan-22 in Escherichia coli dihydrofolate reductase by site-directed mutagenesis. Biochemistry. 1991 Nov 19;30(46):11092-103.
REF 7 The effect of denaturants on protein structure. Protein Sci. 1997 Aug;6(8):1727-33.
REF 8 Expression, characterization and crystallographic analysis of telluromethionyl dihydrofolate reductase. Acta Crystallogr D Biol Crystallogr. 1995 Sep 1;51(Pt 5):731-9.
REF 9 Functional significance of evolving protein sequence in dihydrofolate reductase from bacteria to humans. Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10159-64.

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