Target Information
| Target General Information | Top | |||||
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| Target ID |
T31751
(Former ID: TTDS00236)
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| Target Name |
Plasmodium DOXP reductoisomerase (Malaria DXR)
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| Synonyms |
IspC; DXR; DXP reductoisomerase; DOXP reductoisomerase; 2-C-Methyl-d-erythritol 4-phosphate synthase; 1-deoxyxylulose-5-phosphate reductoisomerase
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| Gene Name |
Malaria DXR
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Malaria [ICD-11: 1F40-1F45] | |||||
| Function |
Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).
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| BioChemical Class |
Short-chain dehydrogenases reductase
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| UniProt ID | ||||||
| EC Number |
EC 1.1.1.267
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| Sequence |
MKKYIYIYFFFITITINDLVINNTSKCVSIERRKNNAYINYGIGYNGPDNKITKSRRCKR
IKLCKKDLIDIGAIKKPINVAIFGSTGSIGTNALNIIRECNKIENVFNVKALYVNKSVNE LYEQAREFLPEYLCIHDKSVYEELKELVKNIKDYKPIILCGDEGMKEICSSNSIDKIVIG IDSFQGLYSTMYAIMNNKIVALANKESIVSAGFFLKKLLNIHKNAKIIPVDSEHSAIFQC LDNNKVLKTKCLQDNFSKINNINKIFLCSSGGPFQNLTMDELKNVTSENALKHPKWKMGK KITIDSATMMNKGLEVIETHFLFDVDYNDIEVIVHKECIIHSCVEFIDKSVISQMYYPDM QIPILYSLTWPDRIKTNLKPLDLAQVSTLTFHKPSLEHFPCIKLAYQAGIKGNFYPTVLN ASNEIANNLFLNNKIKYFDISSIISQVLESFNSQKVSENSEDLMKQILQIHSWAKDKATD IYNKHNSS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Fosmidomycin | Drug Info | Approved | Malaria | [2] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Fosclin | Drug Info | Phase 3 | Malaria | [3] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Fosmidomycin | Drug Info | [1], [4] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Fosclin | Drug Info | [5] | |||
| Drug Binding Sites of Target | Top | |||||
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| 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 | [6] |
| 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 | [6] |
| 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 | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the cata... J Biol Chem. 2003 May 16;278(20):18401-7. | |||||
| REF 2 | The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71. | |||||
| REF 3 | ClinicalTrials.gov (NCT00214643) Efficacy of Fosmidomycin-Clindamycin for Treating Malaria in Gabonese Children. U.S. National Institutes of Health. | |||||
| REF 4 | The apicoplast as an antimalarial drug target. Drug Resist Updat. 2001 Jun;4(3):145-51. | |||||
| REF 5 | Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children. J Infect Dis. 2004 Mar 1;189(5):901-8. | |||||
| REF 6 | Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum. Sci Rep. 2011;1:9. | |||||
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