1f9x
From Proteopedia
(New page: 200px<br /> <applet load="1f9x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f9x" /> '''AVERAGE NMR SOLUTION STRUCTURE OF THE BIR-3...) |
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'''AVERAGE NMR SOLUTION STRUCTURE OF THE BIR-3 DOMAIN OF XIAP'''<br /> | '''AVERAGE NMR SOLUTION STRUCTURE OF THE BIR-3 DOMAIN OF XIAP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The inhibitor of apoptosis proteins (IAPs) regulate the caspase family of | + | The inhibitor of apoptosis proteins (IAPs) regulate the caspase family of cysteine proteases, which play an important role in the execution of programmed cell death. Human X-linked inhibitor of apoptosis protein (XIAP) is a potent inhibitor of caspases-3, -7, and -9. Here we show that the Bir3 domain is the minimal region of XIAP that is needed for potent caspase-9 inhibition. The three-dimensional structure of the Bir3 domain of XIAP, determined by NMR spectroscopy, resembles a classical zinc finger and consists of five alpha-helices, a three-stranded beta-sheet, and a zinc atom chelated to three cysteines and one histidine. The structure of the Bir3 domain is similar to that of the Bir2 domain of XIAP but differs from the previously determined structure of the Bir3 domain of MIHB. Based on site-directed mutagenesis, we have identified the regions of the Bir3 domain of XIAP that are important for inhibiting caspase-9. Despite the structural similarities of the Bir2 and Bir3 domain of XIAP, a different set of residues were found to be critical for inhibiting the individual caspases. These results suggest that XIAP inhibits caspase-3 and caspase-9 in a different manner. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1F9X 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 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1F9X 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> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F9X OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cai, M.]] | [[Category: Cai, M.]] | ||
| - | [[Category: Fesik, S | + | [[Category: Fesik, S W.]] |
| - | [[Category: Meadows, R | + | [[Category: Meadows, R P.]] |
[[Category: Sun, C.]] | [[Category: Sun, C.]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: zinc finger]] | [[Category: zinc finger]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:36:27 2008'' |
Revision as of 10:36, 21 February 2008
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AVERAGE NMR SOLUTION STRUCTURE OF THE BIR-3 DOMAIN OF XIAP
Contents |
Overview
The inhibitor of apoptosis proteins (IAPs) regulate the caspase family of cysteine proteases, which play an important role in the execution of programmed cell death. Human X-linked inhibitor of apoptosis protein (XIAP) is a potent inhibitor of caspases-3, -7, and -9. Here we show that the Bir3 domain is the minimal region of XIAP that is needed for potent caspase-9 inhibition. The three-dimensional structure of the Bir3 domain of XIAP, determined by NMR spectroscopy, resembles a classical zinc finger and consists of five alpha-helices, a three-stranded beta-sheet, and a zinc atom chelated to three cysteines and one histidine. The structure of the Bir3 domain is similar to that of the Bir2 domain of XIAP but differs from the previously determined structure of the Bir3 domain of MIHB. Based on site-directed mutagenesis, we have identified the regions of the Bir3 domain of XIAP that are important for inhibiting caspase-9. Despite the structural similarities of the Bir2 and Bir3 domain of XIAP, a different set of residues were found to be critical for inhibiting the individual caspases. These results suggest that XIAP inhibits caspase-3 and caspase-9 in a different manner.
Disease
Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[300079]
About this Structure
1F9X is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
NMR structure and mutagenesis of the third Bir domain of the inhibitor of apoptosis protein XIAP., Sun C, Cai M, Meadows RP, Xu N, Gunasekera AH, Herrmann J, Wu JC, Fesik SW, J Biol Chem. 2000 Oct 27;275(43):33777-81. PMID:10934209
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