Carbon Monoxide. Toxic Gas and Fuel for Anaerobes and Aerobes: Carbon Monoxide Dehydrogenases - The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment - page 43

Figure 2 Active
and inactive states of
molybdenum hydroxylases.
The CODH and XO/XDH
active sites are converted
by cyanolysis of the sulfide-
ligand to the same inactive
state. CODH: Cu,
Mo-containing carbon
monoxide dehydrogenase;
XO: xanthine oxidase;
XDH: xanthine
dehydrogenase.

According to their sequence and structure Cu,Mo-CODHs belong to the molyb-
denum hydroxylases. Molybdenum hydroxylases typically catalyze the hydroxyl-
ation of activated C-H bonds by coupling the formal transfer of a hydride ion to a
Mo

S bond to the attack of a Mo-bound oxo/hydroxo group on the activated
carbon atom of the substrate. Variations exist in molybdenum hydroxylases isolated
from anaerobic bacteria, which can contain a terminal Mo

¼

¼ Se group instead of the

Mo S group [ 46 ]. Before the Cu ion was identified, Cu,Mo-CODHs were thought

to be dependent on the presence of selenium in the active site [ 47 - 49 ].
Cu,Mo-CODHs share the sequence motif VAYXCSFR found in their active site
loop, where C denotes the cysteine residue binding the Cu ion, the most prominent
distinguishing feature of Cu,Mo-CODHs when compared to other molybdenum
hydroxylases [ 44 , 49 , 50 ]. A group of enzymes closely related to the canonical
Cu,Mo-CODHs called CoxL-II type enzymes is distinct by the lack of the Cu-binding
cysteine residue in the active site [ 9 ]. The physiological function of CoxL-II type
enzymes is not established, but the CoxL-II enzyme from Bradyrhizobium
japonicum USDA 110 was reported to oxidize CO, albeit 10-1000 times slower
than the Cu,Mo-CODH from Oligotropha carboxydovorans [ 51 ].

¼

2.1.1 Structure of Cu,Mo-Carbon Monoxide Dehydrogenases

Cu,Mo-CODHs are typically encoded by three genes. The transcriptional order
in Oligotropha carboxydovorans is coxM-coxS-coxL , encoding for subunits
with 288, 166, and 809 amino acids, respectively. The Cu,Mo-CODH of
O. carboxydovorans is the most extensively investigated Cu,Mo-CODH and all
further discussions relate to this enzyme unless otherwise noted.
The structure of the O. carboxydovorans Cu,Mo-CODH has been determined in
different states and refined to a resolution of 1.09 [ 49 , 50 ], while the structure of

the enzyme from H. pseudoflava has been refined to a resolution of 2.2

Å

[ 52 ].
Both structures show a butterfly shaped dimer of heterotrimers (Figure 3 ). Each of
the three subunits harbors one type of cofactor. The large L subunit carries the
molybdopterin cytosine dinucleotide (MCD) cofactor, which is part of the active

Å