1oxq
From Proteopedia
(New page: 200px<br /> <applet load="1oxq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1oxq, resolution 2.30Å" /> '''Structure and Funct...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1oxq. | + | [[Image:1oxq.jpg|left|200px]]<br /><applet load="1oxq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1oxq" size=" | + | |
caption="1oxq, resolution 2.30Å" /> | caption="1oxq, resolution 2.30Å" /> | ||
'''Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)'''<br /> | '''Structure and Function Analysis of Peptide Antagonists of Melanoma Inhibitor of Apoptosis (ML-IAP)'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1OXQ 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 P33 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1OXQ 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=P33:'>P33</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OXQ OCA]. |
==Reference== | ==Reference== | ||
| Line 30: | Line 29: | ||
[[Category: zinc binding]] | [[Category: zinc binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:37:05 2008'' |
Revision as of 14:37, 15 February 2008
|
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 with and as ligands. 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
Page seeded by OCA on Fri Feb 15 16:37:05 2008
