Serine Proteases Part 2
Index to Course Material
Index to Section 12
Enzymes Index;
Part 1
Part 3
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.
- Trypsin prefers the positively charged Lys and Arg side chains
- Chymotrypsin prefers large hydrophobic side chains (Phe, Tyr, Trp)
- Elastase prefers small hydrophobic side chains such as Ala
This specificity depends on the size and nature of the three residues which
form the specificity pocket, described subsequently.
Index to Course Material
Index to Section 12
Enzymes Index;
Part 1
Part 3
Last updated 10th Jul '96