Methods in Molecular Biology • 16 Enzymes of Molecular Biology

(Nancy Kaufman) #1

(^278) Sweeney and Walker
Table 1
Major Cleavage Sites of Some Proteolytic Enzymes
Enzymes Cleavage site
Chymotrypsin
Clostripain
Elastase
Endoproteinase Arg-C
Endoproteinase Asp-N
Endoproteinase Glu-C
Endoproteinase Lys-C
Pepsin
Thermolysin
Trypsin
C-terminal to hydrophobic residues, e.g., Phe, Tyr,
Trp, Leu
C-terminal to Arg residues
C-terminal to amino acids with small hydrophobic
side chains
C-terminal to Arg residues
N-terminal to Asp and Cys
C-terminal to Asp and Glu
C-terminal to Lys
Broad specificity; preference for cleavage
C-terminal to Phe, Leu, and Glu
N-terminal to amino acids with bulky hydrophobic
side-chains, e.g., Ileu, Leu, Val, and Phe
C-terminal to Lys and Arg
bonds are available to the proteases (i.e., those on the surface of the
protein). This chapter describes ten proteolytic enzymes that have
found extensive use in peptide production in recent years. These are
chymotrypsin, clostripain, elastase, endoproteinase Arg-C (submaxil-
lary protease), endoproteinase Asp-N, endoproteinase Glu-C (V8
protease), endoproteinase Lys-C, pepsin, thermolysin, and trypsin.
The specificities of these enzymes are summarized in Table 1.



  1. Enzyme Data
    2.1. Chymotrypsin (EC 3.4.21.1)
    2.1.1. General Information
    The enzyme is initially synthesized in the pancreas as the inactive
    zymogen chymotrypsinogen. Chymotrypsinogen is converted to the
    active enzyme by cleavage by other proteolytic enzymes when pancreatic
    juice passes into the small intestine. Tryptic cleavage of the bond between
    Arg 15 and Ileu 16 results in a fully active enzyme (n-chymotrypsin).
    Further chymotryptic cleavage between Leu 13 and Ser 14 liberates
    the dipeptide Ser 14-Arg 15, and results in the formation of 8-chymo-
    trypsin (1). Further chymotryptic cleavage liberates the dipeptide Thr
    147-Asn 148 resulting in the commonly used and commercially avail-
    able form of the enzyme, a-chymotrypsin (2). Chymotrypsin is known

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