2az5: Difference between revisions

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[[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="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="2az5, resolution 2.100Å" />

'''Crystal Structure of TNF-alpha with a small molecule inhibitor'''<br />

==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.

==Disease==

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==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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2AZ5 OCA].

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==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: He, M.M.]]

[[Category: He, M M.]]

[[Category: 307]]

[[Category: tnf-alpha trimer disruption by binding of a small molecule inhibitor]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 20~~:56:~~24 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:33 2008''

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@@ 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="450" color="white" frame="true" align="right" spinBox="true"
 caption="2az5, resolution 2.100&Aring;" />
 '''Crystal Structure of TNF-alpha with a small molecule inhibitor'''<br />
 ==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.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-AZ5 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AZ5 OCA].
+AZ5 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==
@@ Line 17: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: He, M.M.]]
+[[Category: He, M M.]]
 [[Category: 307]]
 [[Category: tnf-alpha trimer disruption by binding of a small molecule inhibitor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:56:24 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:33 2008''