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 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 N-({4-[(2-Amino-6-Ethyl-4-Oxo-3,4-Dihydrothieno[2,3-D]pyrimidin-5-Yl)sulfanyl]phenyl}carbonyl)-L-Glutamic Acid Ligand Info
Canonical SMILES CCC1=C(C2=C(S1)N=C(NC2=O)N)SC3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
InChI 1S/C20H20N4O6S2/c1-2-12-15(14-17(28)23-20(21)24-18(14)32-12)31-10-5-3-9(4-6-10)16(27)22-11(19(29)30)7-8-13(25)26/h3-6,11H,2,7-8H2,1H3,(H,22,27)(H,25,26)(H,29,30)(H3,21,23,24,28)/t11-/m0/s1
InChIKey RSFXTHIRRXEJJD-NSHDSACASA-N
PubChem Compound ID 44201386
Drug Binding Sites of Target  Top
PDB ID: 3GHC      Design, Synthesis, and X-ray Crystal Structure of Classical and Nonclassical 2-amino-4-oxo-5-substituted-6-thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agenst
Method X-ray diffraction Resolution 1.30 Å Mutation Yes [1]
PDB Sequence
VGSLNCIVAV
10
SQNMGIGKNG
20
DLPWPPLRNE
30
FRYFSRMTTT
40
SSVEGKQNLV
50

IMGKKTWFSI
60
PEKSRPLKGR
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
3.529
VAL8
3.467
ALA9
3.568
LEU22
3.551
ARG28
4.749
GLU30
2.802
PHE31
3.336
ARG32
3.528
TYR33
4.597
PHE34
3.442
SER35
3.372
Residue
Distance (Å)
THR56
3.616
ILE60
3.871
PRO61
4.044
SER64
3.518
LEU67
3.642
LYS68
4.334
ARG70
2.837
VAL115
3.271
TYR121
3.797
THR136
3.687
PDB ID: 3GHV      Human dihydrofolate reductase Q35K/N64F double mutant inhibitor complex
Method X-ray diffraction Resolution 1.30 Å Mutation Yes [1]
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
3.747
VAL8
3.598
ALA9
3.458
LEU22
3.457
GLU30
2.704
PHE31
3.411
ARG32
4.946
TYR33
4.583
PHE34
3.203
LYS35
3.508
THR38
4.979
Residue
Distance (Å)
THR56
3.618
ILE60
3.885
PRO61
4.187
PHE64
3.483
LEU67
3.707
LYS68
4.532
ARG70
2.857
VAL115
3.354
TYR121
4.171
THR136
3.657
References  Top
REF 1 Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual th... J Med Chem. 2009 Aug 13;52(15):4892-902.

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