Chemistry Reference
In-Depth Information
TABLE 12.1
Coordination Motifs in Catalytic Sites of Some Typical
Mononuclear Zinc Enzymes
Carbonic anhydrase
His-X-His-X
22
-His
b-lactamase
His-X-His-X
121
-His
Thermolysin
His-X
3
-His-X
19
-Glu
Carboxypeptidase
His-X
2
-Glu-X
123
-His
Alcohol dehydrogenase
Cys-X
20
-His-X
106
-Cys
Alkaline phosphatase
Asp-X
3
-His-X
80
-His
Adenosine deaminase
His-X-His-X
196
-His
The mechanism of action of mononuclear zinc enzymes depends on the Zn
2
รพ
-OH
2
centre, which can
participate in the catalytic cycle in three distinct ways (
Figure 12.2
)
either by ionisation, to give zinc-bound
hydroxyl ion (in carbonic anhydrase), polarisation by a general base (in carboxypeptidase), or displacement of
e
OH
-
HO-H---base
Zn
+2
Zn
+2
OH
2
Zn
+2
ionisation
polarisation
substrate
Zn
+2
displacement
FIGURE 12.2
The zinc-bound water can either be ionised to zinc-bound hydroxide, polarised by a general base to generate a nucleophile for
catalysis or displaced by the substrate.
the
OH
2
ligand by the substrate (in alkaline phosphatase). In the first two examples of mononuclear zinc
enzymes which we consider, the lyases (carbonic anhydrase) and the hydrolases (carboxypeptidase), the zinc ion
functions as a powerful electrophilic catalyst by providing some or all of the following properties: (i) an activated
water molecule for nucleophilic attack, (ii) polarisation of the carbonyl of the bond to be cleaved, and (iii) sta-
bilisation of the negative charge which develops in the transition state.
e
Carbonic Anhydrase
The carbonic anhydrases of mammalian erythrocytes have been the object of extensive study for the last 66 years,
and can be considered as the prototype of zinc enzymes which use the hydroxyl ion generated by ionisation of the
