2az5
From Proteopedia
(New page: 200px<br /> <applet load="2az5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2az5, resolution 2.100Å" /> '''Crystal Structure ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2az5.gif|left|200px]]<br /> | + | [[Image:2az5.gif|left|200px]]<br /><applet load="2az5" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2az5" size=" | + | |
caption="2az5, resolution 2.100Å" /> | caption="2az5, resolution 2.100Å" /> | ||
'''Crystal Structure of TNF-alpha with a small molecule inhibitor'''<br /> | '''Crystal Structure of TNF-alpha with a small molecule inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have identified a small-molecule inhibitor of tumor necrosis factor | + | 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== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2AZ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 307 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2AZ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=307:'>307</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZ5 OCA]. |
==Reference== | ==Reference== | ||
| Line 17: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: He, M | + | [[Category: He, M M.]] |
[[Category: 307]] | [[Category: 307]] | ||
[[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:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:33 2008'' |
Revision as of 14:32, 21 February 2008
|
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 with as ligand. 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 Feb 21 16:32:33 2008
