Target Binding Site Detail

Content Navigation (  All   None )                                      
Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T17345 Target Info
Target Name Dihydrofolate reductase (DHFR)
Synonyms DYR; DHFRP1
Target Type Successful Target
Gene Name DHFR
Biochemical Class CH-NH donor oxidoreductase
UniProt ID
DYR_HUMAN
Ligand General Information  Top
Ligand Name Trimethoprim Ligand Info
Canonical SMILES COC1=CC(=CC(=C1OC)OC)CC2=CN=C(N=C2N)N
InChI 1S/C14H18N4O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18)
InChIKey IEDVJHCEMCRBQM-UHFFFAOYSA-N
PubChem Compound ID 5578
Drug Binding Sites of Target  Top
PDB ID: 2W3A      HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND TRIMETHOPRIM
Method X-ray diffraction Resolution 1.50 Å Mutation No [1]
PDB Sequence
VGSLNCIVAV
10
SQNMGIGKNG
20
DLPWPPLRNE
30
FRYFQRMTTT
40
SSVEGKQNLV
50

IMGKKTWFSI
60
PEKNRPLKGR
70
INLVLSRELK
80
EPPQGAHFLS
90
RSLDDALKLT
100

EQPELANKVD
110
MVWIVGGSSV
120
YKEAMNHPGH
130
LKLFVTRIMQ
140
DFESDTFFPE
150

IDLEKYKLLP
160
EYPGVLSDVQ
170
EEKGIKYKFE
180
VYEKND
Residue
Distance (Å)
ILE7
3.232
VAL8
3.499
ALA9
3.662
LEU22
4.056
GLU30
2.685
PHE31
3.042
TYR33
4.580
PHE34
3.540
Residue
Distance (Å)
MET52
4.717
THR56
3.488
ILE60
3.614
PRO61
3.810
LEU67
4.180
VAL115
3.997
TYR121
3.629
THR136
3.684
PDB ID: 3S3V      human dihydrofolate reductase Q35K/N64F double mutant binary complex with trimethoprim
Method X-ray diffraction Resolution 1.53 Å Mutation Yes [2]
PDB Sequence
VGSLNCIVAV
10
SQNMGIGKNG
20
DLPWPPLRNE
30
FRYFKRMTTT
40
SSVEGKQNLV
50

IMGKKTWFSI
60
PEKFRPLKGR
70
INLVLSRELK
80
EPPQGAHFLS
90
RSLDDALKLT
100

EQPELANKVD
110
MVWIVGGSSV
120
YKEAMNHPGH
130
LKLFVTRIMQ
140
DFESDTFFPE
150

IDLEKYKLLP
160
EYPGVLSDVQ
170
EEKGIKYKFE
180
VYEKND
Residue
Distance (Å)
ILE7
3.208
VAL8
3.453
ALA9
3.625
GLY20
3.789
ASP21
3.580
LEU22
3.834
PRO26
4.220
GLU30
2.724
PHE31
3.497
TYR33
4.463
PHE34
3.243
LYS35
3.322
Residue
Distance (Å)
MET52
4.404
THR56
3.705
SER59
3.308
ILE60
3.502
PRO61
3.338
LYS63
4.257
PHE64
3.567
LEU67
3.507
VAL115
3.624
TYR121
3.837
THR136
3.558
PDB ID: 3N0H      hDHFR double mutant Q35S/N64F Trimethoprim Binary Complex
Method X-ray diffraction Resolution 1.92 Å Mutation Yes [2]
PDB Sequence
VGSLNCIVAV
10
SQNMGIGKNG
20
DLPWPPLRNE
30
FRYFSRMTTT
40
SSVEGKQNLV
50

IMGKKTWFSI
60
PEKFRPLKGR
70
INLVLSRELK
80
EPPQGAHFLS
90
RSLDDALKLT
100

EQPELANKVD
110
MVWIVGGSSV
120
YKEAMNHPGH
130
LKLFVTRIMQ
140
DFESDTFFPE
150

IDLEKYKLLP
160
EYPGVLSDVQ
170
EEKGIKYKFE
180
VYEKND
Residue
Distance (Å)
ILE7
3.184
VAL8
3.360
ALA9
3.509
GLY20
4.013
ASP21
3.473
LEU22
4.454
PRO26
4.356
GLU30
2.621
PHE31
3.112
TYR33
4.388
PHE34
3.100
SER35
4.191
Residue
Distance (Å)
MET52
4.351
THR56
3.666
SER59
3.169
ILE60
3.403
PRO61
3.304
LYS63
3.513
PHE64
3.528
LEU67
3.446
VAL115
3.512
TYR121
3.874
THR136
3.454
References  Top
REF 1 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND TRIMETHOPRIM
REF 2 Crystallographic analysis reveals a novel second binding site for trimethoprim in active site double mutants of human dihydrofolate reductase. J Struct Biol. 2011 Oct;176(1):52-9.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.