Transcript Mechanism of action of trypsin and chymotrypsin

Mechanism of action of trypsin
and chymotrypsin
• In the digestive system, trypsin, chymotrypsin
and elastase work as a team.
• All are endopeptidases, which means that they
cleave protein chain at internal peptide bonds
adjacent to particular type of amino acids.
Specificity
• In both trypsin and chymotrypsin,
the side chain of substrate fits into
a pocket. At the far end of this
pocket.
• In trypsin there is negatively
charged aspartic acid residue which
tends to bind through COO- group
to the positively charged side chain
of lysine and arginine.
• Trypsin cuts next to basic amino
acid residues e.g lysine or arginine.
• Chymotrypsin cuts just to aromatic residues as
phenyl alanine, tyrosine and tryptophane.
• Elastase preferes small hydrophobic
residues like alanine.
• Trypsin, Chymotrypsin and elastase are
structurally similar (i.e have similar crystal
structure).
• Small set of amino acid residues come
together in the folded structure to be
essential of the active site catalysis.
These are:
- His 57
-Asp 102
- Ser 195
• Studies show that the reactivity of ser 195 is
not due to a property of serine residue itself
but depends on the special surroundings of
this residue which is His 57 and aspartic 102.
which make serine specially reactive.
• Histidine 57 sits nearby, in an orientation
suggesting that OH group of ser 195 forms
hydrogen bond with the imidazole side chain.
• Aspartic acid sits in the opposite site of the
imidazole ring, where the negatively charged
carboxylic group can interact with the
hydrogen proton on the nitrogen of the ring.
This orientation
helps the removal
of the proton from
serin’s OH group.
Mechanism
Detailed mechanism will be illustrated on the
board to be more clear