1g3f
From Proteopedia
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|PDB= 1g3f |SIZE=350|CAPTION= <scene name='initialview01'>1g3f</scene> | |PDB= 1g3f |SIZE=350|CAPTION= <scene name='initialview01'>1g3f</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g3f OCA], [http://www.ebi.ac.uk/pdbsum/1g3f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1g3f RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The inhibitor-of-apoptosis proteins (IAPs) regulate programmed cell death by inhibiting members of the caspase family of enzymes. Recently, a mammalian protein called Smac (also named DIABLO) was identified that binds to the IAPs and promotes caspase activation. Although undefined in the X-ray structure, the amino-terminal residues of Smac are critical for its function. To understand the structural basis for molecular recognition between Smac and the IAPs, we determined the solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac. The peptide binds across the third beta-strand of the BIR3 domain in an extended conformation with only the first four residues contacting the protein. The complex is stabilized by four intermolecular hydrogen bonds, an electrostatic interaction involving the N terminus of the peptide, and several hydrophobic interactions. This structural information, along with the binding data from BIR3 and Smac peptide mutants reported here, should aid in the design of small molecules that may be used for the treatment of cancers that overexpress IAPs. | The inhibitor-of-apoptosis proteins (IAPs) regulate programmed cell death by inhibiting members of the caspase family of enzymes. Recently, a mammalian protein called Smac (also named DIABLO) was identified that binds to the IAPs and promotes caspase activation. Although undefined in the X-ray structure, the amino-terminal residues of Smac are critical for its function. To understand the structural basis for molecular recognition between Smac and the IAPs, we determined the solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac. The peptide binds across the third beta-strand of the BIR3 domain in an extended conformation with only the first four residues contacting the protein. The complex is stabilized by four intermolecular hydrogen bonds, an electrostatic interaction involving the N terminus of the peptide, and several hydrophobic interactions. This structural information, along with the binding data from BIR3 and Smac peptide mutants reported here, should aid in the design of small molecules that may be used for the treatment of cancers that overexpress IAPs. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300079 300079]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sun, C.]] | [[Category: Sun, C.]] | ||
[[Category: Wu, J C.]] | [[Category: Wu, J C.]] | ||
| - | [[Category: ZN]] | ||
[[Category: apoptosis]] | [[Category: apoptosis]] | ||
[[Category: bir]] | [[Category: bir]] | ||
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[[Category: zinc finger]] | [[Category: zinc finger]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:35:44 2008'' |
Revision as of 17:35, 30 March 2008
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR STRUCTURE OF A 9 RESIDUE PEPTIDE FROM SMAC/DIABLO COMPLEXED TO THE BIR3 DOMAIN OF XIAP
Overview
The inhibitor-of-apoptosis proteins (IAPs) regulate programmed cell death by inhibiting members of the caspase family of enzymes. Recently, a mammalian protein called Smac (also named DIABLO) was identified that binds to the IAPs and promotes caspase activation. Although undefined in the X-ray structure, the amino-terminal residues of Smac are critical for its function. To understand the structural basis for molecular recognition between Smac and the IAPs, we determined the solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac. The peptide binds across the third beta-strand of the BIR3 domain in an extended conformation with only the first four residues contacting the protein. The complex is stabilized by four intermolecular hydrogen bonds, an electrostatic interaction involving the N terminus of the peptide, and several hydrophobic interactions. This structural information, along with the binding data from BIR3 and Smac peptide mutants reported here, should aid in the design of small molecules that may be used for the treatment of cancers that overexpress IAPs.
About this Structure
1G3F is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain., Liu Z, Sun C, Olejniczak ET, Meadows RP, Betz SF, Oost T, Herrmann J, Wu JC, Fesik SW, Nature. 2000 Dec 21-28;408(6815):1004-8. PMID:11140637
Page seeded by OCA on Sun Mar 30 20:35:44 2008
Categories: Homo sapiens | Protein complex | Betz, S F. | Fesik, S W. | Herrmann, J. | Liu, Z. | Meadows, R P. | Olejniczak, E T. | Oost, T. | Sun, C. | Wu, J C. | Apoptosis | Bir | Complex | Peptide-protein | Zinc finger
