Sandbox Reserved 496: Difference between revisions

Mechanism 1 suggests that CO created at the C-cluster travels through the hydrophobic tunnel and binds to Cu.  Next, the A-cluster switches to an open corrinoid conformation so that the methyl group may be transferred from the corrinoid iron-sulfur protein to the distal Ni ion of the active site.  The cluster reverts back to a solvent protected, closed form to generate the acetyl intermediate, and then reopens to allow HSCoA to bind.  HSCoA likely binds in the large cavity between the three domains of the α subunit where six Arg residues and Trp418 coincide.  Finally, HSCoA is deprotonated and acetylated to form acetyl-CoA <ref name="Cu"/>.

Mechanism 2 proposes that CO binds to the proximal Ni ion after exiting the tunnel.  The A-cluster then changes from the closed to the open conformation which closes the hydrophobic CO tunnel and provides a site for methyl group binding on the proximal Ni as it transitions from Ni(0) to Ni(II).  Next, the bound CO inserts into the Ni-CH3 bond to produce an acetyl intermediate.  Lastly, deprotonated CoA-S- attacks the carbonyl carbon of the acetyl group to produce acetyl-CoA and the proximal Ni is reduced back to Ni(0) <ref name="Zn"/>.  Note that this mechanism differs from the former by binding both CO and CH3 to the proximal metal ion and also the A-cluster stays open between methylation and CoA acetylation.

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In the proposed catalytic action of the C-cluster, CO first binds the Ni ion followed by deprotonation of the Fe-bound water to yield a reactive hydroxide which promotes nucleophilic attack of CO by the hydroxide.  Next, the Ni-COOH intermediate is deprotonated to Ni-COO- which allows release of CO2 as the C-cluster is reduced to a new redox state.  Then, electrons are shuttled between the B- and D-clusters to reoxidize the C-cluster to its original redox state <ref name="CN"/>.  This catalytic cycle is of course operated in reverse to reduce CO2 to CO and allow subsequent production of acetyl-CoA .

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