Chemistry Reference
In-Depth Information
Chapter 12
Zinc
e
Lewis Acid and Gene Regulator
Introduction
229
Mononuclear Zinc Enzymes
230
Multinuclear and Cocatalytic Zinc Enzymes
238
Zinc Fingers DNA- and RNA-Binding Motifs
244
INTRODUCTION
Zinc has a highly concentrated charge in comparison to its relatively small ionic radius (0.65
˚
) and binds
modestly to anions such as carboxylates and phosphates. Its second characteristic is its high affinity for electrons,
making it a strong Lewis acid, similar to copper and nickel. However, unlike the other two transition metal ions, it
does not show variable valence, which might lead to it being preferred quite simply because it does not introduce
the risk of free radical reactions.
After iron, zinc is the second most abundant trace element in the human body. An average adult has about 3 g
of Zn, corresponding to a concentration of zinc of about 0.6 mM, most of which (some 95%) is intracellular. Zinc
is essential for growth and development in all forms of life, has been proposed to have beneficial therapeutic and
preventative effects on infectious diseases, including a shortening of the length of the common cold in man.
Zinc is found in more than 300 enzymes, where it plays both a catalytic and a structural role. It is the
only metal to have representatives in each of the six fundamental classes of enzymes recognised by the
International Union of Biochemistry: oxidoreductases like alcohol dehydrogenase and superoxide dis-
mutase; transferases like RNA polymerase and aspartate transcarbamoylase; hydrolases like carboxypep-
tidase A and thermolysin; lyases like carbonic anhydrase and fructose-1,6-bisphosphate aldolase; isomerases
like phosphomannose isomerase; and ligases like pyruvate carboxylase and aminoacyl-tRNA synthases. Zinc
is not only involved in enzymes, where it plays both a catalytic and a structural role. There are growing
numbers of nucleic acid binding proteins with essential Zn atoms, demonstrating the extensive role that Zn
plays in the regulation of the transcription and translation of the genetic message (for more information
concerning the content of this Chapter see
Auld, 2001; Brown, 2005; McCall et al., 2000; Voet and Voet,
2004
).
The bioinorganic chemistry of zinc is dominated by a number of factors, the most pertinent of which are
summarised here. The divalent zinc ion is redox inactive, in contrast, for example, to manganese, iron, and copper.
Its d
10
configuration means that not only does it have no d
d transitions, and therefore no absorption spectroscopy,
but also its complexes are not subject to ligand field stabilisation effects such that Zn
2
þ
has no ligand field
constraints on its coordination geometry. Coordination number and geometry are therefore dictated only by ligand
size and charge. This means that zinc can, in principle, adopt highly flexible coordination geometry. However, in
most zinc proteins, there is a strong preference for tetrahedral coordination, frequently slightly distorted, which
enhances both the Lewis acidity of the zinc centre and the acidity of a coordinated water molecule. Only Cu(II) is
a better Lewis acid. A few cases of zinc in five coordinate distorted trigonal bipyramidal geometry have been
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