(Logo) Serine Proteases Part 2

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Tertiary structure of the Chymotrypsin Superfamily

The homologous enzymes chymotrypsin, trypsin and elastase consist of two similar domains, each of which is a six-stranded antiparallel beta barrel (for a description of this type of fold, refer to the page in Section 10). Some of the loops between the strands include helical sections.


The two domains are different colours

Recall that chymotrypsin consists of three chains, due to several cleavages of the initial zymogen polypeptide. These chains are joined by disulphide bonds. Trypsin on the other hand is a single chain, as the zymogen is activated by removal of the first six residues. There is a marked difference between the conformation of four regions (called the activation domain ) of the trypsin polypeptide compared to its zymogen (Stroud et al, 1977; Huber and Bode, 1978).

Substrates of serine proteases

Proteases are all hydrolases - i.e. they cleave bonds by hydrolysis. (The hydrolases entry of the Enzyme Structures Database, Roman Laskowski and Andrew Wallace Biomolecular Structure and Modelling Group, University College London). Proteases are so named because they hydrolyse peptide bonds; however the chymotrypsin superfamily of serine proteases also cleave ester bonds of certain synthetic substrates.

Although the serine proteases have no absolute specificity, they have strong preferences for the peptide bonds adjacent to specific amino acid residues. The important side chain is the one preceding the scissile bond (i.e. the one which is cleaved) in the sequence, that is, R in the above diagram.

This specificity depends on the size and nature of the three residues which form the specificity pocket, described subsequently. 
IndexIndex to Course MaterialIndexIndex to Section 12SubIndexEnzymes Index; Part 1Part 1Part 3Part 3

Last updated 10th Jul '96