Structure
Cysteine-302 is one of three consecutive Cys residues and is crucial to the enzyme’s catalytic function. The residue is alkylated by iodoacetamide in both the cytosolic and mitochondrial isozymes, with modifications to Cys-302 indicative of catalytic activity with other residues. Furthermore, the preceding sequence Gln-Gly-Gln-Cys is conserved in both isozymes for both human and horse, which is consistent with Cys-302 being crucial to catalytic function.
As discovered by site-directed mutagenesis, glutamate-268 is a key component of liver acetaldehyde dehydrogenase and is also critical to catalytic activity. Since activity in mutants could not be restored by addition of general bases, it’s suggested that the residue functions as a general base for activation of the essential Cys-302 residue.
In bacteria, acylating acetaldehyde dehydrogenase forms a bifunctional heterodimer with metal-dependent 4-hydroxy-2-ketovalerate aldolase. Utilized in the bacterial degradation of toxic aromatic compounds, the enzyme’s crystal structure indicates that intermediates are shuttled directly between active sites through a hydrophobic intermediary channel, providing an unreactive environment in which to move the reactive acetaldehyde intermediate from the aldolase active site to the acetaldehyde dehydrogenase active site. Such communication between proteins allows for the efficient transfer substrates from one active site to the next.
Read more about this topic: Acetaldehyde Dehydrogenase
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