1tw6
From Proteopedia
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|PDB= 1tw6 |SIZE=350|CAPTION= <scene name='initialview01'>1tw6</scene>, resolution 1.713Å | |PDB= 1tw6 |SIZE=350|CAPTION= <scene name='initialview01'>1tw6</scene>, resolution 1.713Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LI:LITHIUM+ION'>LI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |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]) | |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]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1oxn|1OXN]], [[1oxq|1OXQ]], [[1oy7|1OY7]], [[1nw9|1NW9]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tw6 OCA], [http://www.ebi.ac.uk/pdbsum/1tw6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tw6 RCSB]</span> | ||
}} | }} | ||
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[[Category: Vucic, D.]] | [[Category: Vucic, D.]] | ||
[[Category: Wallweber, H J.A.]] | [[Category: Wallweber, H J.A.]] | ||
| - | [[Category: BTB]] | ||
| - | [[Category: EDO]] | ||
| - | [[Category: LI]] | ||
| - | [[Category: ZN]] | ||
[[Category: apoptosis inhibition]] | [[Category: apoptosis inhibition]] | ||
[[Category: peptide complex]] | [[Category: peptide complex]] | ||
[[Category: zinc binding]] | [[Category: zinc binding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:01:58 2008'' |
Revision as of 21:01, 30 March 2008
| |||||||
| , resolution 1.713Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | BIRC7 (Homo sapiens), DIABLO, SMAC (Homo sapiens) | ||||||
| Related: | 1OXN, 1OXQ, 1OY7, 1NW9
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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 Mon Mar 31 00:01:58 2008
