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 Furo[2,3d]Pyrimidine antifolate Ligand Info
Canonical SMILES CN(CC1=COC2=NC(=NC(=C12)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
InChI 1S/C20H22N6O6/c1-26(8-11-9-32-18-15(11)16(21)24-20(22)25-18)12-4-2-10(3-5-12)17(29)23-13(19(30)31)6-7-14(27)28/h2-5,9,13H,6-8H2,1H3,(H,23,29)(H,27,28)(H,30,31)(H4,21,22,24,25)/t13-/m0/s1
InChIKey WXINNGCGSCFUCR-ZDUSSCGKSA-N
PubChem Compound ID 158376
Drug Binding Sites of Target  Top
PDB ID: 1HFP      COMPARISON OF TERNARY CRYSTAL COMPLEXES OF HUMAN DIHYDROFOLATE REDUCTASE WITH NADPH AND A CLASSICAL ANTITUMOR FUROPYRIMDINE
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [1]
PDB Sequence
VGSLNCIVAV
10
SQNMGIGKNG
20
DLPWPPLRNE
30
GRYFQRMTTT
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
3.122
VAL8
3.370
ALA9
3.707
LEU22
3.842
ARG28
4.361
GLU30
2.695
GLY31
3.211
ARG32
3.700
TYR33
4.729
PHE34
3.351
GLN35
3.529
Residue
Distance (Å)
THR56
4.599
SER59
3.505
ILE60
3.752
PRO61
3.775
ASN64
3.067
LEU67
3.473
LYS68
4.665
ARG70
2.544
VAL115
3.323
TYR121
3.598
THR136
3.464
PDB ID: 1HFQ      COMPARISON OF TERNARY CRYSTAL COMPLEXES OF HUMAN DIHYDROFOLATE REDUCTASE WITH NADPH AND A CLASSICAL ANTITUMOR FUROPYRIMDINE
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [1]
PDB Sequence
VGSLNCIVAV
10
SQNMGIGKNG
20
DLPWPPLRNE
30
SRYFQRMTTT
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
3.251
VAL8
3.400
ALA9
3.593
LEU22
4.082
ARG28
4.735
GLU30
2.718
SER31
2.833
ARG32
4.164
TYR33
4.810
PHE34
3.492
GLN35
2.977
Residue
Distance (Å)
THR56
4.680
SER59
3.805
ILE60
3.651
PRO61
3.799
ASN64
2.927
LEU67
3.569
LYS68
4.782
ARG70
2.668
VAL115
3.441
TYR121
3.687
THR136
3.511
PDB ID: 1HFR      COMPARISON OF TERNARY CRYSTAL COMPLEXES OF HUMAN DIHYDROFOLATE REDUCTASE WITH NADPH AND A CLASSICAL ANTITUMOR FUROPYRIMDINE
Method X-ray diffraction Resolution 2.10 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
3.133
VAL8
3.630
ALA9
3.668
LEU22
3.655
GLU30
2.726
PHE31
3.085
ARG32
4.753
TYR33
4.731
PHE34
3.357
GLN35
3.349
THR56
4.586
Residue
Distance (Å)
SER59
3.451
ILE60
3.917
PRO61
4.179
ASN64
2.883
LEU67
3.617
LYS68
4.750
ARG70
2.249
VAL115
3.400
TYR121
3.729
THR136
3.574
References  Top
REF 1 Comparison of ternary crystal complexes of F31 variants of human dihydrofolate reductase with NADPH and a classical antitumor furopyrimidine. Anticancer Drug Des. 1998 Jun;13(4):307-15.

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