Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T61400 | Target Info | |||
| Target Name | Dihydroorotate dehydrogenase (DHODH) | ||||
| Synonyms | Dihydroorotate oxidase; Dihydroorotate dehydrogenase (quinone), mitochondrial; DHOdehase; DHODH | ||||
| Target Type | Successful Target | ||||
| Gene Name | DHODH | ||||
| Biochemical Class | CH-CH donor oxidoreductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Undecylamine-n,n-dimethyl-n-oxide | Ligand Info | |||
| Canonical SMILES | CCCCCCCCCCC[N+](C)(C)[O-] | ||||
| InChI | 1S/C13H29NO/c1-4-5-6-7-8-9-10-11-12-13-14(2,3)15/h4-13H2,1-3H3 | ||||
| InChIKey | OZHBUVQCJMARBN-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 4112111 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3KVL Crystal structure of human dihydroorotate dehydrogenase (DHODH) with amino-benzoic acid inhibitor 715 at 1.85A resolution | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [1] |
| PDB Sequence |
FYAEHLMPTL
46 QGLLDPESAH56 RLAVRFTSLG66 LLPRARFQDS76 DMLEVRVLGH86 KFRNPVGIAA 96 GFDKHGEAVD106 GLYKMGFGFV116 EIGSVTPKPQ126 EGNPRPRVFR136 LPEDQAVINR 146 YGFNSHGLSV156 VEHRLRARQQ166 KQAKLTEDGL176 PLGVNLGKNK186 TSVDAAEDYA 196 EGVRVLGPLA206 DYLVVNVSSP216 NTAGLRSLQG226 KAELRRLLTK236 VLQERDGLRR 246 VHRPAVLVKI256 APDLTSQDKE266 DIASVVKELG276 IDGLIVTNTT286 VSRPAGLQGA 296 LRSETGGLSG306 KPLRDLSTQT316 IREMYALTQG326 RVPIIGVGGV336 SSGQDALEKI 346 RAGASLVQLY356 TALTFWGPPV366 VGKVKRELEA376 LLKEQGFGGV386 TDAIGADHR |
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| PDB ID: 4JTU Crystal structure of human dihydroorotate dehydrogenase (DHODH) with brequinar analogue | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [2] |
| PDB Sequence |
TGDERFYAEH
41 LMPTLQGLLD51 PESAHRLAVR61 FTSLGLLPRA71 RFQDSDMLEV81 RVLGHKFRNP 91 VGIAAGFDKH101 GEAVDGLYKM111 GFGFVEIGSV121 TPKPQEGNPR131 PRVFRLPEDQ 141 AVINRYGFNS151 HGLSVVEHRL161 RARQQKQAKL171 TEDGLPLGVN181 LGKNKTSVDA 191 AEDYAEGVRV201 LGPLADYLVV211 NVSSPNTAGL221 RSLQGKAELR231 RLLTKVLQER 241 DGLRRVHRPA251 VLVKIAPDLT261 SQDKEDIASV271 VKELGIDGLI281 VTNTTVSRPA 291 GLQGALRSET301 GGLSGKPLRD311 LSTQTIREMY321 ALTQGRVPII331 GVGGVSSGQD 341 ALEKIRAGAS351 LVQLYTALTF361 WGPPVVGKVK371 RELEALLKEQ381 GFGGVTDAIG 391 ADHRR
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| PDB ID: 3KVJ Crystal Structure of Human Dihydroorotate Dehydrogenase (DHODH) with Amino-Benzoic Acid Inhibitor 105 at 1.94A Resolution | ||||||
| Method | X-ray diffraction | Resolution | 1.94 Å | Mutation | No | [1] |
| PDB Sequence |
GDERFYAHLM
43 PTLQGLLDPE53 SAHRLAVRFT63 SLGLLPRARF73 QDSDMLEVRV83 LGHKFRNPVG 93 IAAGFDKHGE103 AVDGLYKMGF113 GFVEIGSVTP123 KPQEGNPRPR133 VFRLPEDQAV 143 INRYGFNSHG153 LSVVEHRLRA163 RQQKQAKLTE173 DGLPLGVNLG183 KNKTSVDAAE 193 DYAEGVRVLG203 PLADYLVVNV213 SSPNTAGLRS223 LQGKAELRRL233 LTKVLQERDG 243 LRRVHRPAVL253 VKIAPDLTSQ263 DKEDIASVVK273 ELGIDGLIVT283 NTTVSRPAGL 293 QGALRSETGG303 LSGKPLRDLS313 TQTIREMYAL323 TQGRVPIIGV333 GGVSSGQDAL 343 EKIRAGASLV353 QLYTALTFWG363 PPVVGKVKRE373 LEALLKEQGF383 GGVTDAIGAD 393 HRR
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| PDB ID: 3KVM Crystal structure of human dihydroorotate dehydrogenase (DHODH) with amino-benzoic acid inhibitor 951 at 2.00A resolution | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
ATGDERFYAE
40 HLMPTLQGLL50 DPESAHRLAV60 RFTSLGLLPR70 ARFQDSDMLE80 VRVLGHKFRN 90 PVGIAAGFDK100 HGEAVDGLYK110 MGFGFVEIGS120 VTPKPQEGNP130 RPRVFRLPED 140 QAVINRYGFN150 SHGLSVVEHR160 LRARQQKQAK170 LTEDGLPLGV180 NLGKNKTSVD 190 AAEDYAEGVR200 VLGPLADYLV210 VNVSSPNTAG220 LRSLQGKAEL230 RRLLTKVLQE 240 RDGLRRVHRP250 AVLVKIAPDL260 TSQDKEDIAS270 VVKELGIDGL280 IVTNTTVSRP 290 AGLQGALRSE300 TGGLSGKPLR310 DLSTQTIREM320 YALTQGRVPI330 IGVGGVSSGQ 340 DALEKIRAGA350 SLVQLYTALT360 FWGPPVVGKV370 KRELEALLKE380 QGFGGVTDAI 390 GADHRR
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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 .DET or .DET2 or .DET3 or :3DET;style chemicals stick;color identity;select .A:53 or .A:56 or .A:57 or .A:101 or .A:125 or .A:126 or .A:127 or .A:131 or .A:133 or .A:147 or .A:150 or .A:151 or .A:152; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3KVK Crystal structure of human dihydroorotate dehydrogenase (DHODH) with amino-benzoic acid inhibitor 641 at 2.05A resolution | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [1] |
| PDB Sequence |
GDERFYAEHL
42 MPTLQGLLDP52 ESAHRLAVRF62 TSLGLLPRAR72 FQDSDMLEVR82 VLGHKFRNPV 92 GIAAGFDKHG102 EAVDGLYKMG112 FGFVEIGSVT122 PKPQEGNPRP132 RVFRLPEDQA 142 VINRYGFNSH152 GLSVVEHRLR162 ARQQKQAKLT172 EDGLPLGVNL182 GKNKTSVDAA 192 EDYAEGVRVL202 GPLADYLVVN212 VSSPNTAGLR222 SLQGKAELRR232 LLTKVLQERD 242 GLRRVHRPAV252 LVKIAPDLTS262 QDKEDIASVV272 KELGIDGLIV282 TNTTVSRPAG 292 LQGALRSETG302 GLSGKPLRDL312 STQTIREMYA322 LTQGRVPIIG332 VGGVSSGQDA 342 LEKIRAGASL352 VQLYTALTFW362 GPPVVGKVKR372 ELEALLKEQG382 FGGVTDAIGA 392 DHRR
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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 .DET or .DET2 or .DET3 or :3DET;style chemicals stick;color identity;select .A:53 or .A:56 or .A:57 or .A:60 or .A:98 or .A:100 or .A:101 or .A:103 or .A:125 or .A:126 or .A:127 or .A:133 or .A:147 or .A:150 or .A:151 or .A:152; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4JGD Crystal structure of human dihydroorotate dehydrogenase (DHODH) with DH03A016 | ||||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [3] |
| PDB Sequence |
GDERFYAEHL
42 MPTLQGLLDP52 ESAHRLAVRF62 TSLGLLPRAR72 FQDSDMLEVR82 VLGHKFRNPV 92 GIAAGFDKHG102 EAVDGLYKMG112 FGFVEIGSVT122 PKPQEGNPRP132 RVFRLPEDQA 142 VINRYGFNSH152 GLSVVEHRLR162 ARQQKQAKLT172 EDGLPLGVNL182 GKNKTSVDAA 192 EDYAEGVRVL202 GPLADYLVVN212 VSSPNTAGLR222 SLQGKAELRR232 LLTKVLQERD 242 GLRRVHRPAV252 LVKIAPDLTS262 QDKEDIASVV272 KELGIDGLIV282 TNTTVSRPAG 292 LQGALRSETG302 GLSGKPLRDL312 STQTIREMYA322 LTQGRVPIIG332 VGGVSSGQDA 342 LEKIRAGASL352 VQLYTALTFW362 GPPVVGKVKR372 ELEALLKEQG382 FGGVTDAIGA 392 DHRR
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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 .DET or .DET2 or .DET3 or :3DET;style chemicals stick;color identity;select .A:53 or .A:56 or .A:57 or .A:60 or .A:100 or .A:101 or .A:125 or .A:126 or .A:127 or .A:133 or .A:147 or .A:150 or .A:151 or .A:152; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6VND Quaternary Complex of human dihydroorotate dehydrogenase (DHODH) with flavin mononucleotide (FMN), orotic acid and AG-636 | ||||||
| Method | X-ray diffraction | Resolution | 1.97 Å | Mutation | No | [4] |
| PDB Sequence |
ATGDERFYAE
39 HLMPTLQGLL49 DPESAHRLAV59 RFTSLGLLPR69 ARFQDSDMLE79 VRVLGHKFRN 89 PVGIAAGFDK99 HGEAVDGLYK109 MGFGFVEIGS119 VTPKPQEGNP129 RPRVFRLPED 139 QAVINRYGFN149 SHGLSVVEHR159 LRARQQKQAK169 LTEDGLPLGV179 NLGKNKTSVD 189 AAEDYAEGVR199 VLGPLADYLV209 VNVSSPNTAG219 LRSLQGKAEL229 RRLLTKVLQE 239 RDGLRRVHRP249 AVLVKIAPDL259 TSQDKEDIAS269 VVKELGIDGL279 IVTNTTVSRP 289 AGLQGALRSE299 TGGLSGKPLR309 DLSTQTIREM319 YALTQGRVPI329 IGVGGVSSGQ 339 DALEKIRAGA349 SLVQLYTALT359 FWGPPVVGKV369 KRELEALLKE379 QGFGGVTDAI 389 GADHR
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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 .DET or .DET2 or .DET3 or :3DET;style chemicals stick;color identity;select .A:52 or .A:55 or .A:56 or .A:59 or .A:99 or .A:100 or .A:124 or .A:125 or .A:126 or .A:132 or .A:137 or .A:138 or .A:139 or .A:140 or .A:146 or .A:149 or .A:150 or .A:151 or .A:289 or .A:290 or .A:306 or .A:307 or .A:308 or .A:309 or .A:310 or .A:311; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLU52
4.049
HIS55
3.871
ARG56
3.257
VAL59
4.306
LYS99
3.572
HIS100
3.047
PRO124
3.697
GLN125
3.319
GLU126
3.498
ARG132
4.637
PRO137
4.866
GLU138
3.392
ASP139
3.634
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1981-4. | ||||
| REF 2 | Crystal structure of human dihydroorotate dehydrogenase (DHODH) with brequinar analogue | ||||
| REF 3 | Crystal structure of human dihydroorotate dehydrogenase (DHODH) with DH03A016 | ||||
| REF 4 | Selective Vulnerability to Pyrimidine Starvation in Hematologic Malignancies Revealed by AG-636, a Novel Clinical-Stage Inhibitor of Dihydroorotate Dehydrogenase. Mol Cancer Ther. 2020 Dec;19(12):2502-2515. | ||||
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