1k88: Difference between revisions

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[[Image:1k88.gif|left|200px]]
[[Image:1k88.png|left|200px]]


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==Overview==
{{ABSTRACT_11701129}}
Apoptosis is primarily executed by active caspases, which are derived from the inactive procaspase zymogens through proteolytic cleavage. Here we report the crystal structures of a caspase zymogen, procaspase-7, and an active caspase-7 without any bound inhibitors. Compared to the inhibitor-bound caspase-7, procaspase-7 zymogen exhibits significant structural differences surrounding the catalytic cleft, which precludes the formation of a productive conformation. Proteolytic cleavage between the large and small subunits allows rearrangement of essential loops in the active site, priming active caspase-7 for inhibitor/substrate binding. Strikingly, binding by inhibitors causes a 180 degrees flipping of the N terminus in the small subunit, which interacts with and stabilizes the catalytic cleft. These analyses reveal the structural mechanisms of caspase activation and demonstrate that the inhibitor/substrate binding is a process of induced fit.


==About this Structure==
==About this Structure==
1K88 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1K88 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb56_1.html Caspases]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K88 OCA].  
1K88 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1K88 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb56_1.html Caspases]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K88 OCA].  
==Reference==
Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding., Chai J, Wu Q, Shiozaki E, Srinivasula SM, Alnemri ES, Shi Y, Cell. 2001 Nov 2;107(3):399-407. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11701129 11701129]
[[Category: Caspases]]
[[Category: Caspases]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protease]]
[[Category: Protease]]
[[Category: Substrate binding]]
[[Category: Substrate binding]]
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