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1tw6
From Proteopedia
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| - | [[Image:1tw6.gif|left|200px]] | + | [[Image:1tw6.gif|left|200px]] |
| - | + | ||
| - | '''Structure of an ML-IAP/XIAP chimera bound to a 9mer peptide derived from Smac''' | + | {{Structure |
| + | |PDB= 1tw6 |SIZE=350|CAPTION= <scene name='initialview01'>1tw6</scene>, resolution 1.713Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=LI:LITHIUM+ION'>LI</scene>, <scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene> and <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= BIRC7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), DIABLO, SMAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of an ML-IAP/XIAP chimera bound to a 9mer peptide derived from Smac''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TW6 is a [ | + | 1TW6 is a [[Protein complex]] structure of sequences 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=1TW6 OCA]. |
==Reference== | ==Reference== | ||
| - | Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP., Vucic D, Franklin MC, Wallweber HJ, Das K, Eckelman BP, Shin H, Elliott LO, Kadkhodayan S, Deshayes K, Salvesen GS, Fairbrother WJ, Biochem J. 2005 Jan 1;385(Pt 1):11-20. PMID:[http:// | + | Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP., Vucic D, Franklin MC, Wallweber HJ, Das K, Eckelman BP, Shin H, Elliott LO, Kadkhodayan S, Deshayes K, Salvesen GS, Fairbrother WJ, Biochem J. 2005 Jan 1;385(Pt 1):11-20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15485396 15485396] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[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 14:24:07 2008'' |
Revision as of 12:24, 20 March 2008
| |||||||
| , resolution 1.713Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | BIRC7 (Homo sapiens), DIABLO, SMAC (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of an ML-IAP/XIAP chimera bound to a 9mer peptide derived from Smac
Overview
ML-IAP (melanoma inhibitor of apoptosis) is a potent anti-apoptotic protein that is strongly up-regulated in melanoma and confers protection against a variety of pro-apoptotic stimuli. The mechanism by which ML-IAP regulates apoptosis is unclear, although weak inhibition of caspases 3 and 9 has been reported. Here, the binding to and inhibition of caspase 9 by the single BIR (baculovirus IAP repeat) domain of ML-IAP has been investigated and found to be significantly less potent than the ubiquitously expressed XIAP (X-linked IAP). Engineering of the ML-IAP-BIR domain, based on comparisons with the third BIR domain of XIAP, resulted in a chimeric BIR domain that binds to and inhibits caspase 9 significantly better than either ML-IAP-BIR or XIAP-BIR3. Mutational analysis of the ML-IAP-BIR domain demonstrated that similar enhancements in caspase 9 affinity can be achieved with only three amino acid substitutions. However, none of these modifications affected binding of the ML-IAP-BIR domain to the IAP antagonist Smac (second mitochondrial activator of caspases). ML-IAP-BIR was found to bind mature Smac with low nanomolar affinity, similar to that of XIAP-BIR2-BIR3. Correspondingly, increased expression of ML-IAP results in formation of a ML-IAP-Smac complex and disruption of the endogenous interaction between XIAP and mature Smac. These results suggest that ML-IAP might regulate apoptosis by sequestering Smac and preventing it from antagonizing XIAP-mediated inhibition of caspases, rather than by direct inhibition of caspases.
About this Structure
1TW6 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP., Vucic D, Franklin MC, Wallweber HJ, Das K, Eckelman BP, Shin H, Elliott LO, Kadkhodayan S, Deshayes K, Salvesen GS, Fairbrother WJ, Biochem J. 2005 Jan 1;385(Pt 1):11-20. PMID:15485396
Page seeded by OCA on Thu Mar 20 14:24:07 2008
Categories: Homo sapiens | Protein complex | Das, K. | Deshayes, K. | Elliott, L O. | Fairbrother, W J. | Franklin, M C. | Kadkhodayan, S. | Salvesen, G S. | Shin, H. | Vucic, D. | Wallweber, H J.A. | BTB | EDO | LI | ZN | Apoptosis inhibition | Peptide complex | Zinc binding
