Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T31751 | Target Info | |||
| Target Name | Plasmodium DOXP reductoisomerase (Malaria DXR) | ||||
| Synonyms | IspC; DXR; DXP reductoisomerase; DOXP reductoisomerase; 2-C-Methyl-d-erythritol 4-phosphate synthase; 1-deoxyxylulose-5-phosphate reductoisomerase | ||||
| Target Type | Successful Target | ||||
| Gene Name | Malaria DXR | ||||
| Biochemical Class | Short-chain dehydrogenases reductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | NADPH | Ligand Info | |||
| Canonical SMILES | C1C=CN(C=C1C(=O)N)C2C(C(C(O2)COP(=O)(O)OP(=O)(O)OCC3C(C(C(O3)N4C=NC5=C(N=CN=C54)N)OP(=O)(O)O)O)O)O | ||||
| InChI | 1S/C21H30N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1,3-4,7-8,10-11,13-16,20-21,29-31H,2,5-6H2,(H2,23,32)(H,36,37)(H,38,39)(H2,22,24,25)(H2,33,34,35)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1 | ||||
| InChIKey | ACFIXJIJDZMPPO-NNYOXOHSSA-N | ||||
| PubChem Compound ID | 5884 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3AU8 Crystal structure of the ternary complex of an isomerase | ||||||
| Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | No | [1] |
| PDB Sequence |
PINVAIFGST
86 GSIGTNALNI96 IRECNKIENV106 FNVKALYVNK116 SVNELYEQAR126 EFLPEYLCIH 136 DKSVYEELKE146 LVKNIKDYKP156 IILCGDEGMK166 EICSSNSIDK176 IVIGIDSFQG 186 LYSTMYAIMN196 NKIVALANKE206 SIVSAGFFLK216 KLLNIHKNAK226 IIPVDSEHSA 236 IFQCLDNNKV246 LKTKCLQDNF256 SKINNINKIF266 LCSSGGPFQN276 LTMDELKNVT 286 SENAKKITID305 SATMMNKGLE315 VIETHFLFDV325 DYNDIEVIVH335 KECIIHSCVE 345 FIDKSVISQM355 YYPDMQIPIL365 YSLTWPDRIK375 TNLKPLDLAQ385 VSTLTFHKPS 395 LEHFPCIKLA405 YQAGIKGNFY415 PTVLNASNEI425 ANNLFLNNKI435 KYFDISSIIS 445 QVLESFNSQK455 VSENSEDLMK465 QILQIHSWAK475 DKATDIYNK
|
|||||
|
|
GLY84
3.158
SER85
3.769
THR86
2.615
GLY87
3.027
SER88
2.979
ILE89
3.042
GLY90
4.637
TYR113
3.329
VAL114
3.359
ASN115
2.998
LYS116
2.622
SER117
2.646
GLU120
4.795
|
|||||
| PDB ID: 3AU9 Crystal structure of the quaternary complex-1 of an isomerase | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
PINVAIFGST
86 GSIGTNALNI96 IRECNKIENV106 FNVKALYVNK116 SVNELYEQAR126 EFLPEYLCIH 136 DKSVYEELKE146 LVKNIKDYKP156 IILCGDEGMK166 EICSSNSIDK176 IVIGIDSFQG 186 LYSTMYAIMN196 NKIVALANKE206 SIVSAGFFLK216 KLLNIHKNAK226 IIPVDSEHSA 236 IFQCLDNNKV246 LKTKCLQDNF256 SKINNINKIF266 LCSSGGPFQN276 LTMDELKNVT 286 SENALKHPKW296 KMGKKITIDS306 ATMMNKGLEV316 IETHFLFDVD326 YNDIEVIVHK 336 ECIIHSCVEF346 IDKSVISQMY356 YPDMQIPILY366 SLTWPDRIKT376 NLKPLDLAQV 386 STLTFHKPSL396 EHFPCIKLAY406 QAGIKGNFYP416 TVLNASNEIA426 NNLFLNNKIK 436 YFDISSIISQ446 VLESFNSQKV456 SENSEDLMKQ466 ILQIHSWAKD476 KATDIYNKHN 486
|
|||||
|
|
GLY84
3.537
SER85
4.123
THR86
2.675
GLY87
2.968
SER88
3.014
ILE89
3.081
GLY90
4.889
TYR113
3.303
VAL114
3.379
ASN115
3.089
LYS116
2.678
SER117
2.752
HIS136
3.265
GLY180
3.321
ILE181
3.307
ASP182
3.425
|
|||||
| PDB ID: 3WQR Crystal structure of pfdxr complexed with inhibitor-12 | ||||||
| Method | X-ray diffraction | Resolution | 1.97 Å | Mutation | No | [2] |
| PDB Sequence |
PINVAIFGST
86 GSIGTNALNI96 IRECNKIENV106 FNVKALYVNK116 SVNELYEQAR126 EFLPEYLCIH 136 DKSVYEELKE146 LVKNIKDYKP156 IILCGDEGMK166 EICSSNSIDK176 IVIGIDSFQG 186 LYSTMYAIMN196 NKIVALANKE206 SIVSAGFFLK216 KLLNIHKNAK226 IIPVDSEHSA 236 IFQCLDNNKV246 LKTKCLQDNF256 SKINNINKIF266 LCSSGGPFQN276 LTMDELKNVT 286 SENALKHPKW296 KMGKKITIDS306 ATMMNKGLEV316 IETHFLFDVD326 YNDIEVIVHK 336 ECIIHSCVEF346 IDKSVISQMY356 YPDMQIPILY366 SLTWPDRIKT376 NLKPLDLAQV 386 STLTFHKPSL396 EHFPCIKLAY406 QAGIKGNFYP416 TVLNASNEIA426 NNLFLNNKIK 436 YFDISSIISQ446 VLESFNSQKV456 SENSEDLMKQ466 ILQIHSWAKD476 KATDIYNKHN 486
|
|||||
|
|
GLY84
3.394
SER85
4.010
THR86
2.425
GLY87
2.938
SER88
2.972
ILE89
2.996
GLY90
4.898
TYR113
3.419
VAL114
3.439
ASN115
3.060
LYS116
2.590
SER117
2.678
HIS136
3.472
GLY180
3.248
ILE181
3.384
|
|||||
| PDB ID: 3AUA Crystal structure of the quaternary complex-2 of an isomerase | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [1] |
| PDB Sequence |
PINVAIFGST
86 GSIGTNALNI96 IRECNKIENV106 FNVKALYVNK116 SVNELYEQAR126 EFLPEYLCIH 136 DKSVYEELKE146 LVKNIKDYKP156 IILCGDEGMK166 EICSSNSIDK176 IVIGIDSFQG 186 LYSTMYAIMN196 NKIVALANKE206 SIVSAGFFLK216 KLLNIHKNAK226 IIPVDSEHSA 236 IFQCLDNNKV246 LKTKCLQDNF256 SKINNINKIF266 LCSSGGPFQN276 LTMDELKNVT 286 SENALKHPKW296 KMGKKITIDS306 ATMMNKGLEV316 IETHFLFDVD326 YNDIEVIVHK 336 ECIIHSCVEF346 IDKSVISQMY356 YPDMQIPILY366 SLTWPDRIKT376 NLKPLDLAQV 386 STLTFHKPSL396 EHFPCIKLAY406 QAGIKGNFYP416 TVLNASNEIA426 NNLFLNNKIK 436 YFDISSIISQ446 VLESFNSQKV456 SENSEDLMKQ466 ILQIHSWAKD476 KATDIYNKHN 486
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .A:84 or .A:85 or .A:86 or .A:87 or .A:88 or .A:89 or .A:90 or .A:113 or .A:114 or .A:115 or .A:116 or .A:117 or .A:120 or .A:136 or .A:179 or .A:180 or .A:181 or .A:182 or .A:183 or .A:185 or .A:203 or .A:204 or .A:205 or .A:206 or .A:231 or .A:232 or .A:297 or .A:298 or .A:299 or .A:300 or .A:302 or .A:360; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
3.374
SER85
4.037
THR86
2.714
GLY87
2.935
SER88
2.831
ILE89
2.759
GLY90
4.674
TYR113
3.349
VAL114
3.576
ASN115
3.032
LYS116
2.599
SER117
2.830
GLU120
4.965
HIS136
3.354
ILE179
4.962
GLY180
3.313
|
|||||
| PDB ID: 3WQQ Crystal structure of PfDXR complexed with inhibitor-3 | ||||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [2] |
| PDB Sequence |
PINVAIFGST
86 GSIGTNALNI96 IRECNKIENV106 FNVKALYVNK116 SVNELYEQAR126 EFLPEYLCIH 136 DKSVYEELKE146 LVKNIKDYKP156 IILCGDEGMK166 EICSSNSIDK176 IVIGIDSFQG 186 LYSTMYAIMN196 NKIVALANKE206 SIVSAGFFLK216 KLLNIHKNAK226 IIPVDSEHSA 236 IFQCLDNNKV246 LKTKCLQDNF256 SKINNINKIF266 LCSSGGPFQN276 LTMDELKNVT 286 SENALKHPKW296 KMGKKITIDS306 ATMMNKGLEV316 IETHFLFDVD326 YNDIEVIVHK 336 ECIIHSCVEF346 IDKSVISQMY356 YPDMQIPILY366 SLTWPDRIKT376 NLKPLDLAQV 386 STLTFHKPSL396 EHFPCIKLAY406 QAGIKGNFYP416 TVLNASNEIA426 NNLFLNNKIK 436 YFDISSIISQ446 VLESFNSQKV456 SENSEDLMKQ466 ILQIHSWAKD476 KATDIYNKHN 486
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .A:84 or .A:85 or .A:86 or .A:87 or .A:88 or .A:89 or .A:90 or .A:113 or .A:114 or .A:115 or .A:116 or .A:117 or .A:136 or .A:180 or .A:181 or .A:182 or .A:183 or .A:185 or .A:203 or .A:204 or .A:205 or .A:206 or .A:231 or .A:232 or .A:297 or .A:298 or .A:299 or .A:302 or .A:360; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
3.288
SER85
3.916
THR86
2.585
GLY87
2.911
SER88
2.984
ILE89
2.986
GLY90
4.999
TYR113
3.297
VAL114
3.494
ASN115
2.985
LYS116
2.716
SER117
2.827
HIS136
3.233
GLY180
3.239
ILE181
3.370
|
|||||
| PDB ID: 3WQS Crystal structure of pfdxr complexed with inhibitor-126 | ||||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [2] |
| PDB Sequence |
PINVAIFGST
86 GSIGTNALNI96 IRECNKIENV106 FNVKALYVNK116 SVNELYEQAR126 EFLPEYLCIH 136 DKSVYEELKE146 LVKNIKDYKP156 IILCGDEGMK166 EICSSNSIDK176 IVIGIDSFQG 186 LYSTMYAIMN196 NKIVALANKE206 SIVSAGFFLK216 KLLNIHKNAK226 IIPVDSEHSA 236 IFQCLDNNKV246 LKTKCLQDNF256 SKINNINKIF266 LCSSGGPFQN276 LTMDELKNVT 286 SENALKHPKW296 KMGKKITIDS306 ATMMNKGLEV316 IETHFLFDVD326 YNDIEVIVHK 336 ECIIHSCVEF346 IDKSVISQMY356 YPDMQIPILY366 SLTWPDRIKT376 NLKPLDLAQV 386 STLTFHKPSL396 EHFPCIKLAY406 QAGIKGNFYP416 TVLNASNEIA426 NNLFLNNKIK 436 YFDISSIISQ446 VLESFNSQKV456 SENSEDLMKQ466 ILQIHSWAKD476 KATDIYNKHN 486
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .B:84 or .B:85 or .B:86 or .B:87 or .B:88 or .B:89 or .B:90 or .B:113 or .B:114 or .B:115 or .B:116 or .B:117 or .B:136 or .B:179 or .B:180 or .B:181 or .B:182 or .B:183 or .B:185 or .B:203 or .B:204 or .B:205 or .B:206 or .B:231 or .B:232 or .B:296 or .B:298 or .B:299 or .B:300 or .B:302 or .B:360; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
3.197
SER85
3.885
THR86
2.416
GLY87
2.999
SER88
2.861
ILE89
3.062
GLY90
4.874
TYR113
3.162
VAL114
3.485
ASN115
2.948
LYS116
2.810
SER117
3.015
HIS136
3.732
ILE179
4.683
GLY180
3.118
ILE181
3.280
|
|||||
| PDB ID: 4GAE Crystal structure of plasmodium dxr in complex with a pyridine-containing inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [3] |
| PDB Sequence |
HHGSKKPINV
80 AIFGSTGSIG90 TNALNIIREC100 NKIENVFNVK110 ALYVNKSVNE120 LYEQAREFLP 130 EYLCIHDKSV140 YEELKELVKN150 IKDYKPIILC160 GDEGMKEICS170 SNSIDKIVIG 180 IDSFQGLYST190 MYAIMNNKIV200 ALANKESIVS210 AGFFLKKLLN220 IHKNAKIIPV 230 DSEHSAIFQC240 LDNNKVIKTK250 CLQDNFSKIN260 NINKIFLCSS270 GGPFQNLTMD 280 ELKNVTSENA290 LKHPKWKMGK300 KITIDSATMM310 NKGLEVIETH320 FLFDVDYNDI 330 EVIVHKECII340 HSCVEFIDKS350 VISQMYYPDM360 QIPILYSLTW370 PDRIKTNLKP 380 LDLAQVSTLT390 FHKPSLEHFP400 CIKLAYQAGI410 KGNFYPTVLN420 ASNEIANNLF 430 LNNKIKYFDI440 SSIISQVLES450 FNSQKVSENS460 EDLMKQILQI470 HSWAKDKATD 480 IYNKHN
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NDP or .NDP2 or .NDP3 or :3NDP;style chemicals stick;color identity;select .A:84 or .A:85 or .A:86 or .A:87 or .A:88 or .A:89 or .A:90 or .A:113 or .A:114 or .A:115 or .A:116 or .A:117 or .A:136 or .A:180 or .A:181 or .A:182 or .A:183 or .A:185 or .A:203 or .A:204 or .A:205 or .A:206 or .A:231 or .A:232 or .A:296 or .A:297 or .A:298 or .A:299 or .A:302 or .A:360; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
3.361
SER85
4.013
THR86
2.734
GLY87
2.768
SER88
2.803
ILE89
2.876
GLY90
4.899
TYR113
3.478
VAL114
3.388
ASN115
2.934
LYS116
2.742
SER117
2.838
HIS136
3.494
GLY180
3.304
ILE181
3.452
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum. Sci Rep. 2011;1:9. | ||||
| REF 2 | Binding modes of reverse fosmidomycin analogs toward the antimalarial target IspC. J Med Chem. 2014 Nov 13;57(21):8827-38. | ||||
| REF 3 | Antimalarial and Structural Studies of Pyridine-containing Inhibitors of 1-Deoxyxylulose-5-phosphate Reductoisomerase. ACS Med Chem Lett. 2013 Feb 14;4(2):278-282. | ||||
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