1sc1
From Proteopedia
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Crystal structure of an active-site ligand-free form of the human caspase-1 C285A mutant
Overview
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.
About this Structure
1SC1 is a Protein complex structure of sequences from Homo sapiens with CL as ligand. Active as Caspase-1, with EC number 3.4.22.36 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 Mon Nov 12 19:12:20 2007
