2az5: Difference between revisions
No edit summary |
No edit summary |
||
| Line 7: | Line 7: | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= TNF, TNFA, TNFSF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TNF, TNFA, TNFSF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|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> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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 Structure== | ==About this Structure== | ||
| Line 26: | Line 26: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: He, M M.]] | [[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 | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:59:18 2008'' | ||