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1oxq

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{{STRUCTURE_1oxq| PDB=1oxq | SCENE= }}
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'''Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)'''
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===Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_12846571}}
==About this Structure==
==About this Structure==
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[[Category: Peptide complex]]
[[Category: Peptide complex]]
[[Category: Zinc binding]]
[[Category: Zinc binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 22:59:18 2008''

Revision as of 19:59, 27 July 2008

Image:1oxq.png

Template:STRUCTURE 1oxq

Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)

Template:ABSTRACT PUBMED 12846571

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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