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1oxq
From Proteopedia
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| - | [[Image:1oxq.jpg|left|200px]] | + | [[Image:1oxq.jpg|left|200px]] |
| - | + | ||
| - | '''Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)''' | + | {{Structure |
| + | |PDB= 1oxq |SIZE=350|CAPTION= <scene name='initialview01'>1oxq</scene>, resolution 2.30Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= BIRC7 OR KIAP OR MLIAP OR LIVIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1OXQ is a [ | + | 1OXQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OXQ OCA]. |
==Reference== | ==Reference== | ||
| - | Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP)., Franklin MC, Kadkhodayan S, Ackerly H, Alexandru D, Distefano MD, Elliott LO, Flygare JA, Mausisa G, Okawa DC, Ong D, Vucic D, Deshayes K, Fairbrother WJ, Biochemistry. 2003 Jul 15;42(27):8223-31. PMID:[http:// | + | Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP)., Franklin MC, Kadkhodayan S, Ackerly H, Alexandru D, Distefano MD, Elliott LO, Flygare JA, Mausisa G, Okawa DC, Ong D, Vucic D, Deshayes K, Fairbrother WJ, Biochemistry. 2003 Jul 15;42(27):8223-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12846571 12846571] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 29: | Line 38: | ||
[[Category: zinc binding]] | [[Category: zinc binding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:17:05 2008'' |
Revision as of 11:17, 20 March 2008
| |||||||
| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | BIRC7 OR KIAP OR MLIAP OR LIVIN (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)
Overview
Melanoma inhibitor of apoptosis (ML-IAP) is a potent anti-apoptotic protein that is upregulated in a number of melanoma cell lines but not expressed in most normal adult tissues. Overexpression of IAP proteins, such as ML-IAP or the ubiquitously expressed X-chromosome-linked IAP (XIAP), in human cancers has been shown to suppress apoptosis induced by a variety of stimuli. Peptides based on the processed N-terminus of Smac/DIABLO can negate the ability of overexpressed ML-IAP or XIAP to suppress drug-induced apoptosis. Such peptides have been demonstrated to bind to the single baculovirus IAP repeat (BIR) of ML-IAP and the third BIR of XIAP with similar high affinities (approximately 0.5 microM). Herein, we use phage-display of naive peptide libraries and synthetic peptides to investigate the peptide-binding properties of ML-IAP-BIR and XIAP-BIR3. X-ray crystal structures of ML-IAP-BIR in complex with Smac- and phage-derived peptides, together with peptide structure-activity-relationship data, indicate that the peptides can be modified to provide increased binding affinity and selectivity for ML-IAP-BIR relative to XIAP-BIR3. For instance, substitution of Pro3' in the Smac-based peptide (AVPIAQKSE) with (2S,3S)-3-methylpyrrolidine-2-carboxylic acid [(3S)-methyl-proline] results in a peptide with 7-fold greater affinity for ML-IAP-BIR and about 100-fold specificity for ML-IAP-BIR relative to XIAP-BIR3.
About this Structure
1OXQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP)., Franklin MC, Kadkhodayan S, Ackerly H, Alexandru D, Distefano MD, Elliott LO, Flygare JA, Mausisa G, Okawa DC, Ong D, Vucic D, Deshayes K, Fairbrother WJ, Biochemistry. 2003 Jul 15;42(27):8223-31. PMID:12846571
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