Abstract
Acetyl coenzyme A synthase (ACS) acts in concert with carbon monoxide dehydrogenase (CODH) to catalyze the formation of acetyl-coenzyme A from CO2-derived CO and CH3 + molecules. Recent crystal structures have shown that the three globular domains constituting the ACS subunit may be arranged in either a closed or an open conformation. A long hydrophobic tunnel network allows diffusion of CO between the CODH and the ACS active sites in the closed form, but it is blocked in the open form. On the other hand, the active site of ACS is only accessible for coenzyme A and the methyl donating protein in the open domain conformation. Although several metal compositions have been observed for this active site, present consensus is that it consists of a Ni-Ni-[Fe4S4] cluster. The observed conformational changes of ACS and the resulting different substrate accessibilities of the catalytic central nickel are reviewed here in the context of a putative CO2/CO tunnel gating mechanism.

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