Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

44 Chapter 3
the hydroxyl groups of serine, threonine and tyrosine, and the carboxylate
groups of aspartate and glutamate. There are examples of each of these groups
being used for nucleophilic catalysis, especially serine, which we shall see in
Chapter 5 used for the serine proteases.
An example of the use of aspartate as a nucleophile is the enzyme haloalkane
dehalogenase from Xanthobacter autotrophicus, which is involved in the
dechlorination of organochlorine chemicals found in industrial waste. This
35-kDa protein contains seven strands of b-sheet arranged centrally with
intervening a-helices. This type of ab structure is found in many hydrolase
enzymes such as the serine proteases discussed in Chapter 5. The catalytic
residues Asp-124 and His-289 are situated on loops at the ends of b-sheets.
The active site cavity of volume 37 Å 3 is lined with hydrophobic residues, which
can form favourable hydrophobic interactions with its non-polar substrates.
Shown in Figure 3.18 is a view of the protein structure, highlighting the active
site catalytic residues. The catalytic mechanism proceeds by displacement of
chloride by Asp-128 residue, to give a covalent ester intermediate, followed by
base-catalysed hydrolysis involving His-289, as shown in Figure 3.19.
Figure 3.18 Structure of haloalkane dehalogenase (PDB Wle 2DHD). Asp-124 and His-289 are
shown in red; the product ethanol is shown in black.