Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T01318 | Target Info | |||
| Target Name | Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase) | ||||
| Synonyms | PFF0160c; Mitochondrially bound dihydroorotate-ubiqui oxidoreductase; Dihydroorotate oxidase of Plasmodium falciparum; Dihydroorotate dehydrogenase of Plasmodium falciparum; DHOdehase of Plasmodium falciparum; DHODase; DHODH of Plasmodium falciparum; DHOD | ||||
| Target Type | Successful Target | ||||
| Gene Name | Malaria DHOdehase | ||||
| Biochemical Class | CH-CH donor oxidoreductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 5-methyl-N-naphthalen-2-yl-1H-[1,2,4]triazolo[1,5-a]pyrimidine-3,8-diium-7-amine | Ligand Info | |||
| Canonical SMILES | CC1=CC(=[N+]2C(=N1)[NH+]=CN2)NC3=CC4=CC=CC=C4C=C3 | ||||
| InChI | 1S/C16H13N5/c1-11-8-15(21-16(19-11)17-10-18-21)20-14-7-6-12-4-2-3-5-13(12)9-14/h2-10H,1H3,(H,17,18,19,20)/p+2 | ||||
| InChIKey | GNJXIZOPHGMAQW-UHFFFAOYSA-P | ||||
| PubChem Compound ID | 49867180 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3I65 Plasmodium falciparum dihydroorotate dehydrogenase bound with triazolopyrimidine-based inhibitor DSM1 | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
SYNPEFFLYD
169 IFLKFCLKYI179 DGEICHDLFL189 LLGKYNILPY199 DTSNDSIYAC209 TNIKHLDFIN 219 PFGVAAGFDK229 NGVCIDSILK239 LGFSFIEIGT249 ITPRGQTGNA259 KPRIFRDVES 269 RSIINSCGFN279 NMGCDKVTEN289 LILFRKRQEE299 DKLLSKHIVG309 VSIGKNKDTV 319 NIVDDLKYCI329 NKIGRYADYI339 AINVSSPNEA357 GKLKNIILSV367 KEEIDNLEKN 377 NIMNDEFLWF417 NTTKKKPLVF427 VKLAPDLNQE437 QKKEIADVLL447 ETNIDGMIIS 457 NTTTQINDIK467 SFENKKGGVS477 GAKLKDISTK487 FICEMYNYTN497 KQIPIIASGG 507 IFSGLDALEK517 IEAGASVCQL527 YSCLVFNGMK537 SAVQIKRELN547 HLLYQRGYYN 557 LKEAIGRKHS567
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| PDB ID: 6E0B Plasmodium falciparum dihydroorotate dehydrogenase C276F mutant bound with triazolopyrimidine-based inhibitor DSM1 | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
NPEFFLYDIF
171 LKFCLKYIDG181 EICHDLFLLL191 GKYNILPYDT201 SNDSIYACTN211 IKHLDFINPF 221 GVAAGFDKNG231 VCIDSILKLG241 FSFIEIGTIT251 PRGQTGNAKP261 RIFRDVESRS 271 IINSFGFNNM281 GCDKVTENLI291 LFRKRQEEDK301 LLSKHIVGVS311 IGKNKDTVNI 321 VDDLKYCINK331 IGRYADYIAI341 NVSSPNTPGL351 RDNQEAGKLK361 NIILSVKEEI 371 DNLEKNNIMN381 DEFLWFNTTK421 KKPLVFVKLA431 PDLNQEQKKE441 IADVLLETNI 451 DGMIISNTTT461 QINDIKSFEN471 KKGGVSGAKL481 KDISTKFICE491 MYNYTNKQIP 501 IIASGGIFSG511 LDALEKIEAG521 ASVCQLYSCL531 VFNGMKSAVQ541 IKRELNHLLY 551 QRGYYNLKEA561 IGRKH
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LEU172
2.383
CYS175
2.834
LEU176
2.198
GLY181
3.244
GLU182
4.734
CYS184
2.873
HIS185
2.159
PHE188
2.698
LEU189
2.578
GLY192
3.883
LEU197
2.323
PHE227
2.751
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural plasticity of malaria dihydroorotate dehydrogenase allows selective binding of diverse chemical scaffolds. J Biol Chem. 2009 Sep 25;284(39):26999-7009. | ||||
| REF 2 | Identification and Mechanistic Understanding of Dihydroorotate Dehydrogenase Point Mutations in Plasmodium falciparum that Confer in Vitro Resistance to the Clinical Candidate DSM265. ACS Infect Dis. 2019 Jan 11;5(1):90-101. | ||||
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