From Proteopedia
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| - | [[Image:1qdu.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1qdu| PDB=1qdu | SCENE= }} | | {{STRUCTURE_1qdu| PDB=1qdu | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-8 WITH THE TRIPEPTIDE KETONE INHIBITOR ZEVD-DCBMK'''
| + | ===CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-8 WITH THE TRIPEPTIDE KETONE INHIBITOR ZEVD-DCBMK=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10508784}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10508784 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10508784}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Grutter, M G.]] | | [[Category: Grutter, M G.]] |
| | [[Category: Cysteine-protease]] | | [[Category: Cysteine-protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:10:28 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:13:21 2008'' |
Revision as of 14:13, 28 July 2008
Template:STRUCTURE 1qdu
CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-8 WITH THE TRIPEPTIDE KETONE INHIBITOR ZEVD-DCBMK
Template:ABSTRACT PUBMED 10508784
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
Page seeded by OCA on Mon Jul 28 17:13:21 2008
