1tft: Difference between revisions
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New page: left|200px<br /> <applet load="1tft" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tft" /> '''NMR Structure of an Antagonists of the XIAP... |
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[[Image:1tft.gif|left|200px]]<br /> | [[Image:1tft.gif|left|200px]]<br /><applet load="1tft" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1tft" size=" | |||
caption="1tft" /> | caption="1tft" /> | ||
'''NMR Structure of an Antagonists of the XIAP-Caspase-9 Interaction Complexed to the BIR3 domain of XIAP'''<br /> | '''NMR Structure of an Antagonists of the XIAP-Caspase-9 Interaction Complexed to the BIR3 domain of XIAP'''<br /> | ||
==Overview== | ==Overview== | ||
Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers | Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1TFT 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 ZN and 997 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1TFT 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=ZN:'>ZN</scene> and <scene name='pdbligand=997:'>997</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TFT OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Al-Assaad, A | [[Category: Al-Assaad, A S.]] | ||
[[Category: Armstrong, R | [[Category: Armstrong, R C.]] | ||
[[Category: Betz, S | [[Category: Betz, S F.]] | ||
[[Category: Deckwerth, T | [[Category: Deckwerth, T L.]] | ||
[[Category: Elmore, S | [[Category: Elmore, S W.]] | ||
[[Category: Fesik, S | [[Category: Fesik, S W.]] | ||
[[Category: Meadows, R | [[Category: Meadows, R P.]] | ||
[[Category: Olejniczak, E | [[Category: Olejniczak, E T.]] | ||
[[Category: Oleksijew, A | [[Category: Oleksijew, A K.]] | ||
[[Category: Oltersdorf, T.]] | [[Category: Oltersdorf, T.]] | ||
[[Category: Oost, T | [[Category: Oost, T K.]] | ||
[[Category: Rosenberg, S | [[Category: Rosenberg, S H.]] | ||
[[Category: Shoemaker, A | [[Category: Shoemaker, A R.]] | ||
[[Category: Sun, C.]] | [[Category: Sun, C.]] | ||
[[Category: Zou, H.]] | [[Category: Zou, H.]] | ||
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[[Category: xiap]] | [[Category: xiap]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:13:03 2008'' | ||
