Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

98 Chapter 5
HO
Transition state
peptide-NH
N
H
O OH
H
O
Inhibitor JG-365
K i = 0.66 nM
Ac-Ser-Leu-Asn-NH
HO H
N
O
Ile-Val-OMe
Figure 5.20 Transition state inhibitor for HIV-1 protease.
have potent anti-viral properties in vivo, so this stategy represents a realistic
hope for development of anti-HIV therapy. Figure 5.17 shows the X-ray crystal
structure of the above inhibitor bound to the active site of HIV-1 protease. This
type of high-resolution data provides a good model for the development of
further inhibitors of this enzyme.
5.3 Esterases and lipases
An important part of food digestion is the breakdown of fats, oils and lipid
content in food. Lipids are largely made up of glycerol esters of long-chain fatty
acids. The digestive system of animals contains high levels of esterase and lipase
enzymes which hydrolyse the ester functional groups of fats and oils. Lipases
are often fat-soluble enzymes which are able to operate at the lipid–water
surface which would otherwise present a physical barrier for a soluble esterase
enzyme.
Several members of the family of esterase and lipase enzymes contain
active site serine groups, and proceed via the same type of mechanism as
chymotrypsin (which is capable of hydrolysing esters as well as amides). Two
notable examples are the enzymes pig liver esterase and porcine pancreatic
lipase which are commercially available in large quantities. These enzymes
have found a number of applications in organic synthesis due to their ability
to hydrolyse a wide range of ester substrates with high stereospeciWcity.
Examples of resolution reactions catalysed by these enzymes were illustrated
in Figures 3.2 and 3.3.
Since these enzymes proceed through a covalent acyl enzyme intermediate,
they are able to catalyse transesteriWcation reactions in which an acyl group is