Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T99009 | Target Info | |||
| Target Name | HUMAN dihydroorotate dehydrogenase (DHODH) | ||||
| Synonyms | Dihydroorotate oxidase; Dihydroorotate dehydrogenase (quinone), mitochondrial; DHOdehase; DHODH | ||||
| Gene Name | DHODH | ||||
| Biochemical Class | CH-CH donor oxidoreductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | L-Dihydroorotic acid | Ligand Info | |||
| Canonical SMILES | C1C(NC(=O)NC1=O)C(=O)O | ||||
| InChI | 1S/C5H6N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h2H,1H2,(H,9,10)(H2,6,7,8,11)/t2-/m0/s1 | ||||
| InChIKey | UFIVEPVSAGBUSI-REOHCLBHSA-N | ||||
| PubChem Compound ID | 439216 | ||||
| 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: 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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| 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 .DOR or .DOR2 or .DOR3 or :3DOR;style chemicals stick;color identity;select .A:100 or .A:120 or .A:145 or .A:146 or .A:147 or .A:148 or .A:149 or .A:150 or .A:212 or .A:214 or .A:215 or .A:216 or .A:217 or .A:284 or .A:285 or .A:303; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6ET4 HUMAN DIHYDROOROTATE DEHYDROGENASE IN COMPLEX WITH NOVEL INHIBITOR | ||||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [2] |
| PDB Sequence |
MATGDERFYA
39 EHLMPTLQGL49 LDPESAHRLA59 VRFTSLGLLP69 RARFQDSDML79 EVRVLGHKFR 89 NPVGIAAGFD99 KHGEAVDGLY109 KMGFGFVEIG119 SVTPKPQEGN129 PRPRVFRLPE 139 DQAVINRYGF149 NSHGLSVVEH159 RLRARQQKQA169 KLTEDGLPLG179 VNLGKNKTSV 189 DAAEDYAEGV199 RVLGPLADYL209 VVNVSSPNTA219 GLRSLQGKAE229 LRRLLTKVLQ 239 ERDGLRRVHR249 PAVLVKIAPD259 LTSQDKEDIA269 SVVKELGIDG279 LIVTNTTVSR 289 PAGLQGALRS299 ETGGLSGKPL309 RDLSTQTIRE319 MYALTQGRVP329 IIGVGGVSSG 339 QDALEKIRAG349 ASLVQLYTAL359 TFWGPPVVGK369 VKRELEALLK379 EQGFGGVTDA 389 IGADHRR
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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 .DOR or .DOR2 or .DOR3 or :3DOR;style chemicals stick;color identity;select .A:100 or .A:120 or .A:145 or .A:146 or .A:147 or .A:148 or .A:149 or .A:150 or .A:212 or .A:214 or .A:215 or .A:216 or .A:217 or .A:284 or .A:285 or .A:303; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6GK0 HUMAN DIHYDROOROTATE DEHYDROGENASE IN COMPLEX WITH CLASS III HISTONE DEACETYLASE INHIBITOR | ||||||
| Method | X-ray diffraction | Resolution | 1.85 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 DHR
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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 .DOR or .DOR2 or .DOR3 or :3DOR;style chemicals stick;color identity;select .A:100 or .A:120 or .A:145 or .A:146 or .A:147 or .A:148 or .A:149 or .A:150 or .A:212 or .A:214 or .A:215 or .A:216 or .A:217 or .A:284 or .A:285 or .A:303; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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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 | A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage. Nat Commun. 2018 Mar 16;9(1):1107. | ||||
| REF 3 | Exploitation of dihydroorotate dehydrogenase (DHODH) and p53 activation as therapeutic targets: A case study in polypharmacology. J Biol Chem. 2020 Dec 25;295(52):17935-17949. | ||||
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