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Proposed reaction pathways for InhA and related oxidoreductases. In a first step, the substrates enoyl-CoA and NADH form an ene-shaped transition state. The observed C2-ene adduct can then be formed either directly through a pericyclic ene reaction or via a enolate formed from direct hydride transfer through a Michael-addition reaction. The C2-ene adduct can then be resolved through an elimination reaction, and the enolate abstracts a proton to form the reduced acyl-CoA product.
