Aldehyde Reductase

Aldehyde reductase is a cytoplasmic protein that is a member of the aldo-keto reductase superfamily, a category of enzymes that are responsible for a wide array of biological functions.  “These include the regulation of the proinflammatory response via the reduction of aldehyde phospholipids, the synthesis of metabolically vital compounds such as prostaglandins, and the modulation and modification of steroids in vivo, which include progesterone signaling in breast mammary cells” (2.)  Aldehyde reductase has high sequential (approximately 65%) and structural homology with another member of this class, aldose reductase, both of which “catalyze the NADPH-dependent reduction of aldehydes, xenobiotic aldehydes, ketones, trioses, and triose phosphates" although aldehyde reductase prefers aromatic aldehydes (2.) 
Aldehyde reductase is a monomeric protein with an alpha/beta-TIM barrel structure, whose C-terminal end, with a loop of residues, is responsible for substrate, cofactor, and inhibitor binding.
The mechanism of this catalytic reaction begins with the binding of the aldehyde substrate to the enzyme:NADPH complex.  A hydride transfer from the nicotinamide ring to the carbonyl of the substrate and the essential addition of a proton from the active site residue Tyr49 forms the hydroxyl group of the alcohol product (1.)  “Release of the alcohol product is followed by an enzyme conformational change, involving in part a nucleotide-clamping loop with release of the oxidized NADP- coenzyme and replacement with NADPH” (1.)  Studies have shown that the nucleotide exchange and subsequent protein conformational change is the rate limiting step in the equivalent reaction of the homologous enzyme aldolase reductase, which leads to the same conclusion for the enzyme of topic. 

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Structural alignment of the Jmol images for aldehyde reductase (2ALR) and aldose reductase (1ADS) shows a considerable level of homology.

*This allows you to visualize the C-terminus, which is colored red.
An example of sequence aligenment between aldehyde and aldose reductases made from the ALIGN website. Double dots represent exact amino acid alignment, whereas single dots show where analogous substitutions have occured.

This Jmol image of the pdb file 1Y1P shows aldehyde reductase complexed with Beta-Nicotinamide Ribose Monophosphate and AMP. Notice the conformational change as compared to the apo-protein illustrated before.