Chemistry Reference
In-Depth Information
TABLE 15.1
H
2
, CO dehydrogenase (CODH) interconverts CO and CO
2
, acetyl-CoA synthetase (ACS) in concert with CODH
converts CO
2
and a methyl group to acetyl-CoA and methyl-CoM reductase (MCR) generates methane.
The remaining Ni enzyme, glyoxylase (GlxI), catalyses the conversion of toxic methylglyoxal, (it can readily
form covalent adducts with DNA) to lactate. Its single octahedrally coordinated Ni
2
þ
acts as a Lewis acid, without
changing valency, which presumably explains why it can be replaced by Zn
2
þ
, for example, in man.
Ni sites in enzymes show considerable adaptability, both in terms of Ni coordination and redox chemistry. The
Ni centre in SOD must be able to span redox potentials from
þ
890 to
160 mV, whereas in MCR and CODH, it
must be able to reach potentials as low as
600 mV. This implies that Ni centres in proteins can carry out redox
chemistry over a potential range of
1.5 V. The low levels of available Ni in natural environments has
necessitated the development of high-affinity Ni uptake systems, together with metallochaperones and regulators
of Ni homeostasis.
w
(i)
Urease
Historically, the earliest Ni-containing enzyme to be described was ureasefromjackbeanmeal,whichwas
crystallised by James Sumner in 1926.
1
However, analytical techniques did not allow urease to be recognised
as a Ni-containing enzyme until 50 years later. Urease catalyses the hydrolysis of urea to ammonia and
carbamate, which spontaneously hydrolyses to give carbonic acid and a second molecule of ammonia. It
plays a key role in nitrogen metabolism in plants and microbes whereas land-dwelling animals excrete urea
as the end product of their nitrogen metabolism; clearly, they do not have urease. The active site (
Figure 15.1
)
contains two Ni ions,
3.5
˚
apart which are bridged by a carbamylated lysine residue. Both Ni ions are
coordinated by two His nitrogen atoms, an oxygen from the bridging carbamyl group, and an oxygen from bound
water. One of the Ni atoms in addition has an oxygen ligand from an Asp residue. CO
2
is required for formation of
the carbamylated Lys bridge between the two Ni atoms, and mutation of this Lys results in loss of activity. The
w
1. James Sumner received the Nobel prize for chemistry in 1946 for the crystallisation of proteins. Richard Willst¨tter, the 1915 chemistry
prizewinner, had proposed that proteins were not enzymes, and that the protein in urease was simply a scaffold for the veritable catalyst. Since
urease is inactive without Ni, he was not so far wrong!
