1qdu
From Proteopedia
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| - | [[Image:1qdu.gif|left|200px]] | + | [[Image:1qdu.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-8 WITH THE TRIPEPTIDE KETONE INHIBITOR ZEVD-DCBMK''' | + | {{Structure |
| + | |PDB= 1qdu |SIZE=350|CAPTION= <scene name='initialview01'>1qdu</scene>, resolution 2.8Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=PHQ:FORMIC ACID BENZYL ESTER'>PHQ</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-8 WITH THE TRIPEPTIDE KETONE INHIBITOR ZEVD-DCBMK''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1QDU is a [ | + | 1QDU is a [[Single protein]] structure of sequence 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=1QDU OCA]. |
==Reference== | ==Reference== | ||
| - | The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis., Blanchard H, Kodandapani L, Mittl PR, Marco SD, Krebs JF, Wu JC, Tomaselli KJ, Grutter MG, Structure. 1999 Sep 15;7(9):1125-33. PMID:[http:// | + | The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis., Blanchard H, Kodandapani L, Mittl PR, Marco SD, Krebs JF, Wu JC, Tomaselli KJ, Grutter MG, Structure. 1999 Sep 15;7(9):1125-33. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10508784 10508784] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: cysteine-protease]] | [[Category: cysteine-protease]] | ||
| - | ''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 13:36:19 2008'' |
Revision as of 11:36, 20 March 2008
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| , resolution 2.8Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-8 WITH THE TRIPEPTIDE KETONE INHIBITOR ZEVD-DCBMK
Contents |
Overview
BACKGROUND: In the initial stages of Fas-mediated apoptosis the cysteine protease caspase-8 is recruited to the cell receptor as a zymogen (procaspase-8) and is incorporated into the death-signalling complex. Procaspase-8 is subsequently activated leading to a cascade of proteolytic events, one of them being the activation of caspase-3, and ultimately resulting in cell destruction. Variations in the substrate specificity of different caspases have been reported. RESULTS: We report here the crystal structure of a complex of the activated human caspase-8 (proteolytic domain) with the irreversible peptidic inhibitor Z-Glu-Val-Asp-dichloromethylketone at 2.8 A resolution. This is the first structure of a representative of the long prodomain initiator caspases and of the group III substrate specificity class. The overall protein architecture resembles the caspase-1 and caspase-3 folds, but shows distinct structural differences in regions forming the active site. In particular, differences observed in subsites S(3), S(4) and the loops involved in inhibitor interactions explain the preference of caspase-8 for substrates with the sequence (Leu/Val)-Glu-X-Asp. CONCLUSIONS: The structural differences could be correlated with the observed substrate specificities of caspase-1, caspase-3 and caspase-8, as determined from kinetic experiments. This information will help us to understand the role of the various caspases in the propagation of the apoptotic signal. The information gained from this investigation should be useful for the design of specific inhibitors.
Disease
Known diseases associated with this structure: Autoimmune lymphoproliferative syndrome, type IIB OMIM:[601763], Breast cancer, protection against OMIM:[601763], Hepatocellular carcinoma, somatic OMIM:[601763], Lung cancer, protection against OMIM:[601763]
About this Structure
1QDU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis., Blanchard H, Kodandapani L, Mittl PR, Marco SD, Krebs JF, Wu JC, Tomaselli KJ, Grutter MG, Structure. 1999 Sep 15;7(9):1125-33. PMID:10508784
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