Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T20178 | Target Info | |||
| Target Name | Tumor necrosis factor (TNF) | ||||
| Synonyms | Tumour necrosis factor alpha; Tumour necrosis factor; Tumor necrosis factor ligand superfamily member 2; TNFalpha; TNFSF2; TNFA; TNF-alpha; TNF-a; TNF alpha; Cachectin | ||||
| Target Type | Successful Target | ||||
| Gene Name | TNF | ||||
| Biochemical Class | Cytokine: tumor necrosis factor | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 4-N-benzyl-4-N-[2-[3-(2-piperazin-1-ylpyrimidin-5-yl)phenyl]phenyl]pyrimidine-2,4-diamine | Ligand Info | |||||
| Structure Description | HUMAN TNF-ALPHA IN COMPLEX WITH JNJ525 | PDB:5MU8 | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [1] |
| PDB Sequence |
SDKPVAHVVA
18 NPQAEGQLQW28 LNALLANGVE42 LRDNQLVVPS52 EGLYLIYSQV62 LFKGQGCPST 72 HVLLTHTISR82 IAVSYQTKVN92 LLSAIKSPCQ102 RETEAKPWYE116 PIYLGGVFQL 126 EKGDRLSAEI136 NRPDYLDFAE146 SGQVYFGIIA156 L
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| Ligand Name: (1-Oxyl-2,2,5,5-tetramethylpyrroline-3-methyl)methanethiosulfonate | Ligand Info | |||||
| Structure Description | Crystal Structure of Spin-Labeled T77C TNFa | PDB:5UUI | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [2] |
| PDB Sequence |
SDKPVAHVVA
18 NPQAEGQLQW28 LNRRANALLA38 NGVELRDNQL48 VVPSEGLYLI58 YSQVLFKGQG 68 VLLCHTISRI83 AVSYQTKVNL93 LSAIKSPAKP113 WYEPIYLGGV123 FQLEKGDRLS 133 AEINRPDYLD143 FAESGQVYFG153 IIAL
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| Ligand Name: 8-[4-(2-{5-[(4-methylpiperazin-1-yl)methyl]-2-(1H-pyrrolo[3,2-c]pyridin-3-yl)phenoxy}ethyl)phenyl]isoquinoline | Ligand Info | |||||
| Structure Description | Crystal Structure of TNFalpha with isoquinoline compound 4 | PDB:6X82 | ||||
| Method | X-ray diffraction | Resolution | 2.75 Å | Mutation | No | [3] |
| PDB Sequence |
SDKPVAHVVA
18 NPQAEGQLQW28 LNRRANALLA38 NGVELRDNQL48 VVPSEGLYLI58 YSQVLFKGQG 68 CPSTHVLLTH78 TISRIAVSYQ88 TKVNLLSAIK98 SPCQREAKPW114 YEPIYLGGVF 124 QLEKGDRLSA134 EINRPDYLDF144 AESGQVYFGI154 IAL
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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 .UTM or .UTM2 or .UTM3 or :3UTM;style chemicals stick;color identity;select .A:11 or .A:57 or .A:59 or .A:60 or .A:61 or .A:119 or .A:120 or .A:121 or .A:122 or .A:151 or .A:155 or .A:156 or .A:157; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: [4-(Isoquinolin-8-yl)phenyl]acetonitrile | Ligand Info | |||||
| Structure Description | Crystal Structure of TNFalpha with isoquinoline compound 2 | PDB:6X81 | ||||
| Method | X-ray diffraction | Resolution | 2.81 Å | Mutation | No | [3] |
| PDB Sequence |
SDKPVAHVVA
18 NPQAEGQLQW28 LNRRANALLA38 NGVELRDNQL48 VVPSEGLYLI58 YSQVLFKGQG 68 CPSTHVLLTH78 TISRIAVSYQ88 TKVNLLSAIK98 SPCQRETPAK112 PWYEPIYLGG 122 VFQLEKGDRL132 SAEINRPDYL142 DFAESGQVYF152 GIIAL
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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 .UTJ or .UTJ2 or .UTJ3 or :3UTJ;style chemicals stick;color identity;select .A:57 or .A:59 or .A:60 or .A:61 or .A:119 or .A:120 or .A:121 or .A:151 or .A:155; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1-Benzyl-1H-benzimidazole | Ligand Info | |||||
| Structure Description | Crystal Structure of TNFalpha with fragment compound 6 | PDB:6X83 | ||||
| Method | X-ray diffraction | Resolution | 2.83 Å | Mutation | No | [3] |
| PDB Sequence |
SDKPVAHVVA
18 NPQAEGQLQW28 LNRRANALLA38 NGVELRDNQL48 VVPSEGLYLI58 YSQVLFKGQG 68 CPSTHVLLTH78 TISRIAVSYQ88 TKVNLLSAIK98 SPCQAKPWYE116 PIYLGGVFQL 126 EKGDRLSAEI136 NRPDYLDFAE146 SGQVYFGIIA156 L
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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 .UTS or .UTS2 or .UTS3 or :3UTS;style chemicals stick;color identity;select .A:57 or .A:58 or .A:59 or .A:120 or .A:121 or .A:122; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 6,7-Dimethyl-3-[(methyl{2-[methyl({1-[3-(trifluoromethyl)phenyl]-1H-indol-3-YL}methyl)amino]ethyl}amino)methyl]-4H-chromen-4-one | Ligand Info | |||||
| Structure Description | Crystal Structure of TNF-alpha with a small molecule inhibitor | PDB:2AZ5 | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [4] |
| PDB Sequence |
DKPVAHVVAN
19 PQAEGQLQWL29 NLLANGVELR44 DNQLVVPSEG54 LYLIYSQVLF64 KGQGCPSTHV 74 LLTHTISRIA84 VSYQTKVNLL94 SAIKSPCPWY115 EPIYLGGVFQ125 LEKGDRLSAE 135 INRPDYLDFA145 ESGQVYFGII155 AL
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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 .307 or .3072 or .3073 or :3307;style chemicals stick;color identity;select .A:57 or .A:58 or .A:59 or .A:60 or .A:61 or .A:119 or .A:120 or .A:121 or .A:122 or .A:151; 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 | Structural Basis of Small-Molecule Aggregate Induced Inhibition of a Protein-Protein Interaction. J Med Chem. 2017 Apr 27;60(8):3511-3517. | ||||
| REF 2 | Natural Conformational Sampling of Human TNFAlpha Visualized by Double Electron-Electron Resonance. Biophys J. 2017 Jul 25;113(2):371-380. | ||||
| REF 3 | Development of Orally Efficacious Allosteric Inhibitors of TNFAlpha via Fragment-Based Drug Design. J Med Chem. 2021 Jan 14;64(1):417-429. | ||||
| REF 4 | Small-molecule inhibition of TNF-alpha. Science. 2005 Nov 11;310(5750):1022-5. | ||||
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