Aldo-keto reductase
Encyclopedia
The aldo-keto reductase family is a family
Protein family
A protein family is a group of evolutionarily-related proteins, and is often nearly synonymous with gene family. The term protein family should not be confused with family as it is used in taxonomy....

 of enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s that includes a number of related monomeric NADPH
Nicotinamide adenine dinucleotide phosphate
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or TPN in older notation , is a coenzyme used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent....

-dependent oxidoreductase
Oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...

s, such as aldehyde reductase, aldose reductase
Aldose reductase
Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides...

, prostaglandin F synthase
Prostaglandin-F synthase
In enzymology, a prostaglandin-F synthase is an enzyme that catalyzes the chemical reaction--9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ \rightleftharpoons --9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+...

, xylose reductase
L-xylose 1-dehydrogenase
In enzymology, a L-xylose 1-dehydrogenase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are L-xylose and NADP+, whereas its 3 products are L-xylono-1,4-lactone, NADPH, and H+....

, rho crystallin, and many others.

Structure

All possess a similar structure, with a beta-alpha-beta fold characteristic of nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

 binding proteins. The fold comprises a parallel beta-8/alpha-8-barrel, which contains a novel NADP-binding motif. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the beta sheet
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...

, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones.

Binding of the NADPH coenzyme causes a massive conformational change, reorienting a loop, effectively locking the coenzyme in place. This binding is more similar to FAD- than to NAD(P)-binding oxidoreductases.

Examples

Some proteins of this family contain a potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...

beta chain regulatory domain; these are reported to have oxidoreductase activity.
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