2az5: Difference between revisions

Revision as of 19:39, 3 May 2008

Crystal Structure of TNF-alpha with a small molecule inhibitor

OverviewOverview

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.

About this StructureAbout this Structure

2AZ5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Sat May 3 19:39:10 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2az5.gif|left|200px]]
- {{Structure
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-|GENE= TNF, TNFA, TNFSF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-|DOMAIN=
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-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2az5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2az5 OCA], [http://www.ebi.ac.uk/pdbsum/2az5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2az5 RCSB]</span>
-}}
 '''Crystal Structure of TNF-alpha with a small molecule inhibitor'''
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 [[Category: Single protein]]
 [[Category: He, M M.]]
-[[Category: tnf-alpha trimer disruption by binding of a small molecule inhibitor]]
+[[Category: Tnf-alpha trimer disruption by binding of a small molecule inhibitor]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 19:39:10 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:59:18 2008''