Short-chain dehydrogenase

The crystal structure of the halohydrin dehalogenase from the soil bacterium Agrobacterium radiobacter ADI, HheC, has been solved [129]. HheC is structurally related to the family of NAD(P)H-dependent short-chain dehydrogenases/reduc-... 

Dihydroflavonol 4-reductase (DFR EC 1.1.1.219) is a member of the short-chain dehydrogenase/reductase family and catalyzes the stereospecific conversion of (+)-(2R,3R)-dihydroflavonols to the corresponding (2R,3S,4S) flavan-3,4-cw-diols (leucoanthocyanidins), with NADPH as a required cofactor. The enzyme activity was first identified in cell suspension cultures of Douglas fir (Pseudotsuga menziesii) and was shown to be related to the accumulation of flavan-3-ols and proanthocyanidins [96]. Leucoanthocyanidins and DFR were later shown to be required for anthocyanidin formation by complementation of Matthiola incana mutants blocked between dihydroflavonol and anthocyanidin biosynthesis [97, 98], DFR has been purified to apparent homogeneity and biochemically analyzed from flower buds of Dahlia variabilis [99]. DFR was shown to accept different substrates depending on the plant species from which it was isolated (reviewed in 100). 

Nakajima, K., Hashimoto, T. and Yamada, N. 1993. Two tropinone reducetases with different stereospecificities are short-chain dehydrogenases evolved from a common ancestor. Proceedings of the National Academy of Sciences of the United States of America, 90 9591-9595. 

DFR belongs to the single-domain-reductase/epimerase/dehydrogenase (RED) protein family, which has also been termed the short chain dehydrogenase/reductase (SDR) superfamily. This contains other flavonoid biosynthetic enzymes, in particular the anthocyanidin reductase (ANR), leucoanthocyanidin reductase (EAR), isoflavone reductase (IFR), and vestitone reductase (VR), as well as mammalian, bacterial, and other plant enzymes. ... 

Lactobacillus brevis also produces an (R)-spedfic ADH (LB-ADH) [4]. These two enzymes have similar properties. An alignment of the protein sequences of both short-chain dehydrogenases revealed an identity of 88% (Fig. 2.2.4.5). The nucleotide sequences of LK-ADH and LB-ADH show an identity of 78%. 

Ribas dePoplana L, Fothergill-Gilmore LA. The active site architecture of a short chain dehydrogenase defined by site-directed mutagenesis and structure modeling. Biochemistry 33 1994 7047-7055. 

The ADH from Lactobacillus brevis (Riebel, 1997) has a broad substrate specificity and converts even bulky aromatic ketones with high activity (Hummel, 1999 Wolberg, 2001). In addition, the enzyme is the best characterized completely (R)-specific ADH. The enzyme belongs to the class of short-chain dehydrogenases and its 3D structure has recently been solved (Niefind, 2003). The recombinant form of L. brevis ADH in E. coli accepts a variety of /j.d-dikelo esters as was determined in the synthesis of potential building blocks for HMG CoA reductase inhibitors (see also Chapter 13, Section 13.3.2) (Wolberg, 2001). tert-Butyl 3,5-dioxohexanoate and tert-butyl 3,5-dioxoheptanoate were reduced on a preparative scale to afford the corresponding (R)-<5-hydroxy-/3-keto esters with 99.4% e.e. and 98.1% e.e., respectively. 

Catalytic Reaction Mechanism of Drosophila ADH, a Short-Chain Dehydrogenase... 

Short-chain dehydrogenases/re-ductases (Figs. 4-6) Total length of ca. 250 residues, Mr 29 kDa All except AadlOp, Yfl057c and Aadl5p 44... 

H Jornvall, B Persson, M Krook, S Atrian, R Gonzalez-Duarte, J Jeffery, D Ghosh. Short-chain dehydrogenases/reductases (SDR). Biochemistry 34 6003-6013,1995. 

Abbreviations. ADH, alcohol dehydrogenase ALDH, aldehyde dehydrogenase AKR, aldo-keto reductases GST, glutathione -transferase MT, methyltransferase SDR, short-chain dehydrogenases/reductases SULT, sulfotransferase UGT, UDP-glucuronosyltransferase. 

Ziegler, J. Voegtlander, S., Schmidt, J., Kramell, R., Miersch, O., Ammer, C., Gesell, A. and Kutchan, T.M. (2006) Comparative transcript and alkaloid profiling in Papaver species identifies a short chain dehydrogenase/reductase involved in morphine biosynthesis. Plant.., 48,177-92. 

Dehydrogenase activity could clearly be separated from a ketosteroid iso-merase (see below) indicating that rDZ3 3-HSD is related to microbial HSDs of the short-chain dehydrogenase/reductase (SDR) family but not with mammalian HSDs, which are multifunctional enz)mies. 

Egerer-Sieber et al. (2006) reported on the purification and crystallization of recombinant 5p-POR from D. lanata. Later on, Gavidia et al. (2007) predicted that the 5p-POR belongs to the SDR family (Oppermann et al, 1997). Finally, Thorn et al. (2008) fully characterized the crystal structure and found that the progesterone reductase from D. lanata defines a novel class of short-chain dehydrogenases / reductases. 

Thorn, A., Egerer-Sieber, C., Jager, C.M., Herl, V., Muller-Uri, R, Kreis, W. and Muller, Y.A. (2008) The crystal structure of progesterone 5p-reductase from Digitalis lanata defines a novel class of short chain dehydrogenases/reductases. /. Biol. Chem., 283, 17260-9. 

Kavanagh, K. L., Jornvall, H., Persson, B., Oppermann, U. (2008). Medium- and short-chain dehydrogenase/reductase gene and protein families the SDR superfamily functional and structural diversity within a family of metabolic and regulatory enzymes. Cellular and Molecular Life Sciences, 65, 3895—3906. 

Short-chain dehydrogenases/ reductases Alcohol dehydrogenases... 

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

Hallborn et al. [115] cloned a short-chain dehydrogenase gene from P. stipitis CBS 6054 that has its highest activity with D-arabinitol as substrate. The D-arabinitol dehydrogenase activity is not induced by xylose but it can use xylitol as a substrate. D-Ribulose is the final product for this enzyme. This enzyme is similar to an NAD+-dependent D-arabitol dehydrogenase cloned from Candida albicans [116]. 

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