Carbon Monoxide. Toxic Gas and Fuel for Anaerobes and Aerobes: Carbon Monoxide Dehydrogenases - The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment - page 61

mechanistic proposal may be that Ni p would need to co-exist next to an oxidized
[4Fe4S] cluster, a combination whose stability has been doubted [ 145 ].
Recently, the diamagnetic mechanism was extended by including the confor-
mational states of ACS [ 143 ]. In the extended mechanism the protein conforma-
tion controls coordination of ligands at cluster A through a conserved
phenylalanine residue that moves into and out of the coordination environment
of Ni p . A phenylalanine to alanine exchange produced an ACS variant with a
substantially decreased reactivity with methylated CoFeSP, while its reactivity
with CO was increased. These results suggest that phenyalanine sterically
determines the favored substrate order (methyl group first) and prevents CO
inhibition.
Thus, despite the existing computational, spectroscopic, kinetic, and crystallo-
graphic studies the mechanism of acetyl-CoA formation at cluster A remains
unresolved and new approaches to the question are required.

2.4 Cu,Mo versus Ni,Fe: Parallels and Differences
in Catalytic Strategies

Cu,Mo-CODHs and Ni,Fe-CODHs catalyze the oxidation of CO, but they
achieve this with two very different active site architectures (Figure 14 ): one
CODH contains Cu and Mo, the other Ni and Fe; one active site has two metals
and one

ʼ 3 -sulfido-
ligands; in Cu,Mo-CODH one of the metals is coordinated by an organic
cofactor and one cysteine, in Ni,Fe-CODHs we find no organic cofactor but
five cysteines and one histidine as coordinating ligands. Thus, in contrast to
enzymes like serine proteases and Zn-dependent carboanhydrases, CODHs
show no signs of convergent evolution to create non-homologous, isofunc-
tional enzymes.

ʼ 2 -sulfido-ligand, the other has five metal ions and four

Figure 14 Catalytic strategies of Cu,Mo- and Ni,Fe-CODH in comparison. Cu (Cu,Mo-CODH)
and Ni (Ni,Fe-CODH) bind and activate CO. The activated nucleophilic water is bound to Mo
(Cu,Mo-CODH) and Fe 1 (Ni,Fe-CODH). Electrons are taken up by Mo (Cu,Mo-CODH), and it is
unknown where the electrons are stored in cluster C.