1tw6

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[[Image:1tw6.gif|left|200px]]<br /><applet load="1tw6" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1tw6.gif|left|200px]]
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caption="1tw6, resolution 1.713&Aring;" />
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'''Structure of an ML-IAP/XIAP chimera bound to a 9mer peptide derived from Smac'''<br />
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{{Structure
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|PDB= 1tw6 |SIZE=350|CAPTION= <scene name='initialview01'>1tw6</scene>, resolution 1.713&Aring;
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|SITE=
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|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>
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|ACTIVITY=
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|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])
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}}
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'''Structure of an ML-IAP/XIAP chimera bound to a 9mer peptide derived from Smac'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1TW6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=LI:'>LI</scene>, <scene name='pdbligand=BTB:'>BTB</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TW6 OCA].
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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==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15485396 15485396]
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:18:00 2008''
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''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

Image:1tw6.gif


PDB ID 1tw6

Drag the structure with the mouse to rotate
, 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

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