Caspases: Their Role in Cell Death and Cell Survival by Marek Los, Henning Walczak

By Marek Los, Henning Walczak

The quantity bargains perception into the most important learn issues that contain caspases. best specialists from a number of parts of biology and medication have compiled this quantity in order that either the beginner and the pro will use this because the major reference for caspases for future years. The reader will know about the function of caspases in apoptosis signaling, irritation and melanoma treatment whereas being up to date at the technique used to check caspases and the efforts of pharmaceutical learn in focusing on caspases.

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6A). Then, Cys285 attacks the P1 amide bond of the substrate thereby inducing formation of the tetrahedral intermediate. At this stage the substrate is covalently attached to the catalytic cysteine that has lost its nucleophilic property (Fig. 6B). Next, the C-terminal peptide of the substrate is released from the complex, while the peptide N-terminal of the scissile bond and the enzyme form an acyl-enzyme complex (Fig. 6C). The oxygen pole of a water molecule, acting as a nucleophile, attacks the carbonyl group of the acyl-enzyme complex and induces a second tetrahedral intermediate (Fig.

In general, caspases can be divided in three groups according to their tetrapeptide substrate specificities. Enzymes from group I (caspase-1, -4 and –5) prefer the sequence WEHD. Group II caspases (caspase-2, -3, -7 and CED-3) prefer DEXD and Group III enzymes (caspase-6, -8, -9 and –11) prefer the tetrapeptide (I/L/V)EXD as a substrate. (adapted from refs. 38,83,136,137) and Table 5). The optimal recognition motif for group III caspases is also similar to activation sites within some of the executioner caspase proenzymes, such as caspase-3 and -7 (Fig.

In addition, a negative charge present in the S4 pocket of caspase-8 is unfavorable for a P4 aspartic acid. Therefore, the caspase-8 S4 pocket is wide but preferentially accommodates aliphatic residues at the P4 position, though other residues are also tolerated. ' These structural motifs have emerged as the prime mediators of the interactions necessary for transducing inflammatory and death signals and can be found in a growing number of proteins involved in apoptosis and inflammation. 30-32 Each of these motifs interacts with other proteins through homotypic interactions.

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