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 Dihydrofolic acid Ligand Info
Canonical SMILES C1C(=NC2=C(N1)N=C(NC2=O)N)CNC3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
InChI 1S/C19H21N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,12,21H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t12-/m0/s1
InChIKey OZRNSSUDZOLUSN-LBPRGKRZSA-N
PubChem Compound ID 135398604
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)
ILE5
2.705
ALA6
3.051
ALA7
2.579
MET20
2.361
TRP22
4.033
PRO25
4.845
ASP27
2.055
LEU28
2.744
ALA29
3.049
TRP30
2.955
PHE31
2.404
LYS32
2.244
THR35
4.510
THR46
2.963
Residue
Distance (Å)
SER49
3.777
ILE50
2.659
ARG52
1.594
LEU54
2.967
PRO55
3.512
ARG57
1.746
ILE94
2.146
GLY95
4.406
TYR100
3.601
TYR111
4.241
LEU112
4.716
THR113
2.627
PHE153
4.445
PDB ID: 1RF7      STRUCTURE OF DIHYDROFOLATE REDUCTASE COMPLEXED WITH DIHYDROFOLATE
Method X-ray diffraction Resolution 1.80 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

YCFEILERR
Residue
Distance (Å)
ILE5
3.356
ALA6
3.278
ALA7
3.451
GLU17
4.771
ASP27
2.686
LEU28
3.549
TRP30
4.161
PHE31
3.296
LYS32
3.490
THR35
4.773
THR46
4.069
ILE50
3.794
ARG52
2.723
Residue
Distance (Å)
LEU54
3.959
PRO55
4.325
ARG57
2.834
ILE94
3.294
TYR100
3.639
THR113
3.332
HIS114
3.026
TYR128
4.940
SER138
3.871
GLU139
4.532
PHE140
3.351
CYS152
2.010
GLU154
2.921
PDB ID: 6MT8      E. coli DHFR complex modeled with two ligand states
Method X-ray diffraction Resolution 1.35 Å Mutation No [3]
PDB Sequence
MISLIAALAV
10
DRVIGMMPWN
23
LPADLAWFKR
33
NTLNKPVIMG
43
RHTWESIGRP
53

LPGRKNIILS
63
SQPGTDDRVT
73
WVKSVDEAIA
83
ACGDVPEIMV
93
IGGGRVYEQF
103

LPKAQKLYLT
113
HIDAEVEGDT
123
HFPDYEPDDW
133
ESVFSEFHDA
143
DAQNSHSYCF
153

EILERRHHH
Residue
Distance (Å)
ILE5
2.063
ALA6
2.811
ALA7
2.597
GLY15
4.002
MET16
2.445
MET20
4.142
TRP22
4.203
PRO25
4.885
ASP27
2.125
LEU28
2.410
TRP30
2.577
PHE31
2.523
LYS32
2.847
THR35
4.354
Residue
Distance (Å)
THR46
2.835
SER49
4.970
ILE50
2.877
LEU54
2.891
PRO55
3.236
ARG57
1.887
ILE94
2.006
GLY95
3.874
TYR100
2.759
TYR111
4.457
LEU112
4.562
THR113
2.594
PHE153
4.386
PDB ID: 6MTH      E. coli DHFR complex modeled with three ligand states
Method X-ray diffraction Resolution 1.35 Å Mutation No [3]
PDB Sequence
MISLIAALAV
10
DRVIGMMPWN
23
LPADLAWFKR
33
NTLNKPVIMG
43
RHTWESIGRP
53

LPGRKNIILS
63
SQPGTDDRVT
73
WVKSVDEAIA
83
ACGDVPEIMV
93
IGGGRVYEQF
103

LPKAQKLYLT
113
HIDAEVEGDT
123
HFPDYEPDDW
133
ESVFSEFHDA
143
DAQNSHSYCF
153

EILERRHHH
Click to Show 3D Structure of This Binding Site
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Residue
Distance (Å)
ILE5
2.063
ALA6
2.811
ALA7
2.597
GLY15
4.002
MET16
2.445
MET20
4.142
TRP22
4.203
PRO25
4.885
ASP27
2.125
LEU28
2.410
TRP30
2.577
PHE31
2.523
LYS32
2.847
THR35
4.354
Residue
Distance (Å)
THR46
2.835
SER49
4.970
ILE50
2.877
LEU54
2.891
PRO55
3.236
ARG57
1.887
ILE94
2.006
GLY95
3.874
TYR100
2.759
TYR111
4.457
LEU112
4.562
THR113
2.594
PHE153
4.386
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 Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. Biochemistry. 1997 Jan 21;36(3):586-603.
REF 3 Time-resolved x-ray crystallography capture of a slow reaction tetrahydrofolate intermediate. Struct Dyn. 2019 Mar 1;6(2):024701.

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