Chemistry Reference
In-Depth Information
(a)
O
2
, 2[e
-
], 2H
+
H
2
O
SH
SOH
(b)
O
O
H
+
, NADH
H
2
O, NAD
+
H
H
N
N
N
N
OH
N
N
O
N
O
N
H
H
H
H
FIGURE 17.1
Reaction stoichiometries for the monooxygenases (a) and molybdenum hydroxylases (b).
(Adapted from
Hille, 2005
.)
the flavin-containing p-hydroxybenzoate hydroxylase to the copper-containing dopamine-
b
-monooxygenase, the
haem-containing cytochromes P-450, and the nonhaem iron-containing methane monooxygenase, which we have
encountered in previous chapters.
If we assume that the early conditions on our planet were not only anaerobic, but hot, tungsten would have
been much better adapted than molybdenum, since low-valent tungsten sulfides would have been more soluble in
aqueous solutions, their tungsten-sulfur bonds more stable, and their reduction potentials lower than their
molybdenum equivalents. As the earth's crust cooled, and cyanobacterial photosynthesis transformed the atmo-
sphere from anaerobic to aerobic, the oxygen-sensitivity of tungsten compounds, together with the greater water-
solubility of high-valence molybdenum oxides, and the dramatically different redox balance, would have pushed
the scales in favour of molybdenum. This hypothesis (
Hille, 2002
)
is supported by the distribution of the two;
molybdenum enzymes are present in all aerobes and tungsten enzymes only in obligate anaerobes (often
thermophiles). A few anaerobes can use either metal, depending on availability.
Another factor which characterises Mo (and W) enzymes is that, with the exception of bacterial nitrogenase,
the FeMo-cofactor of which will be discussed later, instead of using the metal itself directly coordinated to amino
acid side chains of the protein, they contain a molybdenum pyranopterindithiolate cofactor (MoCo), which is the
active component of their catalytic site. The cofactor (pyranopterindithiolate) coordinates the metal ion via
a dithiolate side chain.
The biosynthetic pathway for this pterin cofactor, which was described in Chapter 4, appears to be universally
conserved in biology, underlining its importance. Interestingly however, baker's yeast, a much used 'model'
eukaryote, is the only organism known which does not contain Mo enzymes (it is also one of the few organisms
which does not contain ferritin). The MoCo cofactor can exist in the fully oxidised (Mo
VI
) and fully reduced
(Mo
IV
) forms, with some enzymes generating the (Mo
V
) form as a catalytic intermediate.
MOLYBDENUM ENZYME FAMILIES
Molybdenum-containing enzymes can be divided into three families, the xanthine oxidase (XO), sulfite oxidase
(SO), and the DMSO reductase (DMR) families. They each have a characteristic active site structure
(
Figure 17.2
(
a)) and catalyse a particular type of reaction (see below). Whereas in eukaryotes, the pterin side chain
has a terminal phosphate group, in prokaryotes, the cofactor (R in
Figure 17.2
(
b)) it is often a dinucleotide.
Of the three members of the XO family, xanthine oxidase/dehydrogenases and aldehyde oxidoreductases
catalyse the hydroxylation of carbon centres, whereas the third family member, the CO dehydrogenase from
Oligotropha carboxidovorans, converts CO to CO
2
. This latter enzyme is a structural exception, in that it has
a dinuclear heterometal [CuSMoO
2
H] cluster, with the sulfido ligand coordinated by the Cu
I
centre (for the
structure of this, see Chapter 4, Figure 4.12).
