Binding Site Information of Target
| 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 | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Fosmidomycin | Ligand Info | |||||
| Structure Description | Crystal structure of the quaternary complex-1 of an isomerase | PDB:3AU9 | ||||
| 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
|
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| Ligand Name: NADPH | Ligand Info | |||||
| Structure Description | Crystal structure of the ternary complex of an isomerase | PDB:3AU8 | ||||
| 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
|
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|
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
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: NADP+ | Ligand Info | |||||
| Structure Description | Structure of Plasmodium IspC in complex with a beta-thia-isostere derivative of Fosmidomycin | PDB:4KP7 | ||||
| Method | X-ray diffraction | Resolution | 2.00 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 KATDIYNKH |
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAP or .NAP2 or .NAP3 or :3NAP;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: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
3.354
SER85
3.989
THR86
2.662
GLY87
2.969
SER88
2.991
ILE89
3.089
TYR113
3.344
VAL114
3.643
ASN115
3.107
LYS116
2.803
SER117
2.834
HIS136
2.978
GLY180
3.312
ILE181
3.384
ASP182
3.298
|
|||||
| Ligand Name: [(1s)-4-[hydroxy(Methyl)amino]-1-(4-Methoxyphenyl)-4-Oxobutyl]phosphonic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of pfdxr complexed with inhibitor-12 | PDB:3WQR | ||||
| Method | X-ray diffraction | Resolution | 1.97 Å | Mutation | No | [3] |
| 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
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LSX or .LSX2 or .LSX3 or :3LSX;style chemicals stick;color identity;select .A:205 or .A:231 or .A:232 or .A:233 or .A:268 or .A:269 or .A:270 or .A:271 or .A:272 or .A:295 or .A:296 or .A:298 or .A:302 or .A:306 or .A:311 or .A:312 or .A:315 or .A:338 or .A:358 or .A:360; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LYS205
3.349
ASP231
2.923
SER232
2.594
GLU233
3.131
CYS268
4.239
SER269
2.984
SER270
2.596
GLY271
4.322
GLY272
4.187
LYS295
3.386
|
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| Ligand Name: (3-(Acetylhydroxyamino)propyl)phosphonic acid | Ligand Info | |||||
| Structure Description | Crystal structure of the quaternary complex-2 of an isomerase | PDB:3AUA | ||||
| 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
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .F98 or .F982 or .F983 or :3F98;style chemicals stick;color identity;select .A:205 or .A:231 or .A:232 or .A:233 or .A:268 or .A:269 or .A:270 or .A:271 or .A:272 or .A:293 or .A:296 or .A:298 or .A:302 or .A:306 or .A:311 or .A:312 or .A:315 or .A:338 or .A:360; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: [(1s)-4-[hydroxy(Methyl)amino]-1-(4-Methylphenyl)-4-Oxobutyl]phosphonic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of PfDXR complexed with inhibitor-3 | PDB:3WQQ | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [3] |
| 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
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .IB3 or .IB32 or .IB33 or :3IB3;style chemicals stick;color identity;select .A:205 or .A:231 or .A:232 or .A:233 or .A:268 or .A:269 or .A:270 or .A:271 or .A:272 or .A:295 or .A:296 or .A:298 or .A:302 or .A:306 or .A:311 or .A:312 or .A:315 or .A:338 or .A:358 or .A:360; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LYS205
3.360
ASP231
2.864
SER232
2.686
GLU233
3.267
CYS268
4.204
SER269
3.006
SER270
2.703
GLY271
4.289
GLY272
4.199
LYS295
3.978
|
|||||
| Ligand Name: [(R)-{2-[hydroxy(Methyl)amino]-2-Oxoethoxy}(4-Methoxyphenyl)methyl]phosphonic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of pfdxr complexed with inhibitor-126 | PDB:3WQS | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [3] |
| 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 .KBK or .KBK2 or .KBK3 or :3KBK;style chemicals stick;color identity;select .B:205 or .B:231 or .B:232 or .B:233 or .B:268 or .B:269 or .B:270 or .B:271 or .B:272 or .B:295 or .B:296 or .B:298 or .B:302 or .B:306 or .B:311 or .B:312 or .B:315 or .B:338 or .B:358 or .B:360; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LYS205
3.283
ASP231
2.887
SER232
2.713
GLU233
2.995
CYS268
4.226
SER269
3.182
SER270
2.773
GLY271
4.228
GLY272
4.271
LYS295
3.569
|
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| Ligand Name: [(S)-({2-[hydroxy(Methyl)amino]-2-Oxoethyl}sulfanyl)(Phenyl)methyl]phosphonic Acid | Ligand Info | |||||
| Structure Description | Structure of Plasmodium IspC in complex with a beta-thia-isostere derivative of Fosmidomycin | PDB:4KP7 | ||||
| Method | X-ray diffraction | Resolution | 2.00 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 KATDIYNKH |
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .1UQ or .1UQ2 or .1UQ3 or :31UQ;style chemicals stick;color identity;select .A:205 or .A:231 or .A:232 or .A:233 or .A:268 or .A:269 or .A:270 or .A:271 or .A:272 or .A:295 or .A:296 or .A:298 or .A:302 or .A:306 or .A:311 or .A:312 or .A:315 or .A:338 or .A:358 or .A:360; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LYS205
3.195
ASP231
2.761
SER232
2.500
GLU233
2.894
CYS268
4.467
SER269
3.056
SER270
2.574
GLY271
4.251
GLY272
4.133
LYS295
3.952
|
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| Ligand Name: [(1r)-3-[acetyl(Hydroxy)amino]-1-(Pyridin-4-Yl)propyl]phosphonic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of plasmodium dxr in complex with a pyridine-containing inhibitor | PDB:4GAE | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [4] |
| 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
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .FOB or .FOB2 or .FOB3 or :3FOB;style chemicals stick;color identity;select .A:205 or .A:231 or .A:232 or .A:233 or .A:268 or .A:269 or .A:270 or .A:271 or .A:272 or .A:293 or .A:296 or .A:298 or .A:302 or .A:306 or .A:311 or .A:312 or .A:315 or .A:338 or .A:358 or .A:360; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LYS205
4.563
ASP231
3.150
SER232
2.900
GLU233
3.517
CYS268
4.408
SER269
3.371
SER270
2.897
GLY271
4.031
GLY272
4.078
HIS293
4.605
|
|||||
| Ligand Name: [(1s)-3-[acetyl(Hydroxy)amino]-1-(Pyridin-4-Yl)propyl]phosphonic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of plasmodium dxr in complex with a pyridine-containing inhibitor | PDB:4GAE | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [4] |
| 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 .FOQ or .FOQ2 or .FOQ3 or :3FOQ;style chemicals stick;color identity;select .A:205 or .A:231 or .A:232 or .A:233 or .A:268 or .A:269 or .A:270 or .A:271 or .A:272 or .A:293 or .A:296 or .A:298 or .A:302 or .A:306 or .A:311 or .A:312 or .A:315 or .A:338 or .A:358 or .A:360; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LYS205
4.751
ASP231
3.206
SER232
2.864
GLU233
3.386
CYS268
4.414
SER269
3.070
SER270
2.688
GLY271
4.224
GLY272
4.572
HIS293
4.708
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum. Sci Rep. 2011;1:9. | ||||
| REF 2 | IspC as target for antiinfective drug discovery: synthesis, enantiomeric separation, and structural biology of fosmidomycin thia isosters. J Med Chem. 2013 Oct 24;56(20):8151-62. | ||||
| REF 3 | Binding modes of reverse fosmidomycin analogs toward the antimalarial target IspC. J Med Chem. 2014 Nov 13;57(21):8827-38. | ||||
| REF 4 | 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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