Sulfite
Oxidase: The Electrostatic Bulls-eye!
by Dr. J. Hazzard
Liver Sulfite Oxidase
(SOX) catalyzes the 2-electron oxidation of
SO32- to
SO42-, transferring the
electrons to 2 oxidized cytochromes c.
The enzyme contains two structurally distinct
domains, a molybdo (Mo)-pterin domain (site of
sulfite oxidation) and a heme domain (site of
cytochrome c reduction). The two domains are
connected by a 19 amino acid loop that is highly
flexible (left figure below). Sulfate
(SO42-), the product of
sulfite oxidation, is shown bound at the Mo-pterin
catalytic site (right figure below).
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The distribution of
charged groups on the surface of SOX, near the
Mo-pterin site is ideal for attracting and binding
the small, negatively charged substrate,
SO32- (left figure below: Red
= -; Blue = +; White = neutral). At the entrance of
a channel leading to the Mo-pterin site, which is
buried within the enzyme, there is a cluster of
three positively charged residues (Arg-138,
Lys-200, Arg 450). These groups give rise to
a strong positive electrostatic potential
(blue). Surrounding this is a neutral
environment (white), while lying more peripherally
is a ring of negatively charged residues
(red). The net effect of this distribution of
charged amino acid side chains is to create an
“Electrostatic Bulls-eye148;, which in both a
repulsive (negative – negative) as well
as positive (plus – negative) manner directs
the small anionic substrate precisely to the
enzyme’s active site. When the product,
SO42-, is bound at the
Mo-pterin active site the positive electrostatic
potential is significantly diminished.
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