2az5
From Proteopedia
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| , resolution 2.100Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | TNF, TNFA, TNFSF2 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of TNF-alpha with a small molecule inhibitor
Contents |
Overview
We have identified a small-molecule inhibitor of tumor necrosis factor alpha (TNF-alpha) that promotes subunit disassembly of this trimeric cytokine family member. The compound inhibits TNF-alpha activity in biochemical and cell-based assays with median inhibitory concentrations of 22 and 4.6 micromolar, respectively. Formation of an intermediate complex between the compound and the intact trimer results in a 600-fold accelerated subunit dissociation rate that leads to trimer dissociation. A structure solved by x-ray crystallography reveals that a single compound molecule displaces a subunit of the trimer to form a complex with a dimer of TNF-alpha subunits.
Disease
Known diseases associated with this structure: Asthma, susceptibility to OMIM:[191160], Dementia, vascular, susceptibility to OMIM:[191160], Malaria, cerebral, susceptibility to OMIM:[191160], Migraine without aura, susceptibility to OMIM:[191160], Septic shock, susceptibility to OMIM:[191160]
About this Structure
2AZ5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Small-molecule inhibition of TNF-alpha., He MM, Smith AS, Oslob JD, Flanagan WM, Braisted AC, Whitty A, Cancilla MT, Wang J, Lugovskoy AA, Yoburn JC, Fung AD, Farrington G, Eldredge JK, Day ES, Cruz LA, Cachero TG, Miller SK, Friedman JE, Choong IC, Cunningham BC, Science. 2005 Nov 11;310(5750):1022-5. PMID:16284179
Page seeded by OCA on Thu Mar 20 15:55:38 2008
