Structure, Mechanism of Action and Inhibition of Dehydrogenase Enzymes

Abstract

The family of short chain dehydrogenase reductase (SDR) enzymes includes over 60 enzymes from humans, mammals, insects and bacteria that have as substrates, steroids, sugars, prostaglandins, alcohols, dyes, and other small molecules. These enzymes typically exhibit only 15 to 30% sequence identity [1]. A small number of highly conserved residues, including an YXXXK sequence, characterize members of the family. There is no significant degree of sequence homology with members of the long chain dehydrogenase family that includes the lactate (LDH), malate (MDH), and D-glyceraldehyde-3-phosphate (GDPH) dehydrogenases [2]. The facts that LDH, MDH and GDPH all had 325–335 amino acids and that the first few members of the SDR family isolated were found to have 240–250 amino acids led to the characterization of the former as long chain dehydrogenases (LCDH) and the later as SDR’s. As a result of the addition of dozens of new members to the SDR family they are seen to vary in total length from 240 to 360 residues overlapping the length of the LCDH’s. Although the two families have no sequence similarity they share common characteristics. Members of both families use NAD(H) and/or NADP(H) as cofactors and both use alcohols as substrates.