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1sc1

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{{STRUCTURE_1sc1| PDB=1sc1 | SCENE= }}
{{STRUCTURE_1sc1| PDB=1sc1 | SCENE= }}
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'''Crystal structure of an active-site ligand-free form of the human caspase-1 C285A mutant'''
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===Crystal structure of an active-site ligand-free form of the human caspase-1 C285A mutant===
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==Overview==
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Caspase-1, a mediator of the posttranslational processing of IL-1beta and IL-18, requires an aspartic acid in the P1 position of its substrates. The mechanisms of caspase-1 activation remain poorly understood despite numerous structures of the enzyme complexed with aspartate-based inhibitors. Here we report a crystal structure of ligand-free caspase-1 that displays dramatic rearrangements of loops defining the active site to generate a closed conformation that is incompatible with substrate binding. A structure of the enzyme complexed with malonate shows the protein in its open (active-site ligand-bound) conformation in which malonate reproduces the hydrogen bonding network observed in structures with covalent inhibitors. These results illustrate the essential function of the obligatory aspartate recognition element that opens the active site of caspase-1 to substrates and may be the determinant responsible for the conformational changes between ligand-free and -bound forms of the enzyme, and suggest a new approach for identifying novel aspartic acid mimetics.
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The line below this paragraph, {{ABSTRACT_PUBMED_15296730}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15296730 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15296730}}
==About this Structure==
==About this Structure==
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[[Category: Scheer, J M.]]
[[Category: Scheer, J M.]]
[[Category: Ligand-free caspase-1]]
[[Category: Ligand-free caspase-1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:31:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:01:56 2008''

Revision as of 09:01, 29 July 2008

Image:1sc1.png

Template:STRUCTURE 1sc1

Crystal structure of an active-site ligand-free form of the human caspase-1 C285A mutant

Template:ABSTRACT PUBMED 15296730

About this Structure

1SC1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding., Romanowski MJ, Scheer JM, O'Brien T, McDowell RS, Structure. 2004 Aug;12(8):1361-71. PMID:15296730

Page seeded by OCA on Tue Jul 29 12:01:56 2008

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