Disease relevance of MGC4172

• Licorice induces high blood pressure by inhibiting an SDR in the kidney, and appears to combat ulcers by inhibiting another in the stomach [1].
• Mutagenetic replacements of conserved residues within the active site of the short-chain dehydrogenase/reductase (SDR) superfamily were studied using prokaryotic 3 beta/17 beta-hydroxysteroid dehydrogenase (3 beta/17 beta-HSD) from Comamonas testosteroni as a model system [2].
• We performed site directed mutagenesis of R28, a basic residue conserved in most NADPH dependent SDR structures; T200, found only in Streptomyces hydrogenans 3alpha,20beta-HSD and Drosophila alcohol dehydrogenases; and H230, a residue corresponding to the substrate specificity important H221 in human 17beta-HSD type 1 [3].

Psychiatry related information on MGC4172

• Binding of amyloid beta-peptide to mitochondrial hydroxyacyl-CoA dehydrogenase (ERAB): regulation of an SDR enzyme activity with implications for apoptosis in Alzheimer's disease [4].

High impact information on MGC4172

• Members of the NADPH-dependent short chain dehydrogenase/reductase (SDR) family control blood pressure, fertility, and natural and neoplastic growth [1].
• By contrast, bioinformatics studies suggested a relationship of CC3 to the short chain dehydrogenase reductase family [5].
• CC3 has a short chain dehydrogenase reductase fold and binding specificity for NADPH, yet it is unlikely to be normally enzymatically active because it is monomeric [5].
• Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of the short chain dehydrogenase/reductase (SDR) family, is responsible for the biosynthesis of all active estrogens [6].
• Type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of the short chain dehydrogenase reductase (SDR) family, is responsible for the synthesis of 17beta-estradiol, the biologically active estrogen involved in the genesis and development of human breast cancers [7].

Biological context of MGC4172

• Amino acid sequence analysis of components III and IV demonstrates that they belong to the short-chain dehydrogenase/reductase (SDR) family of enzymes [8].
• These sequences matched a previously uncharacterized EST in The Institute for Genome Research (TIGR) zebrafish database that is related to the short-chain dehydrogenase/reductase (SDR) protein family [9].
• Both components contain highly conserved residues within the coenzyme binding fold and catalytic regions found in SDR enzymes [8].
• The intracellular amyloid beta-peptide (A beta) binding protein, ERAB, a member of the short-chain dehydrogenase/reductase (SDR) family, is known to mediate apoptosis in different cell lines and to be a class II hydroxyacyl-CoA dehydrogenase [4].
• These data extend the insight that a subfamily of SDR isozymes, tissue-distinctively expressed, catalyzes the first step in RA biogenesis [10].

Anatomical context of MGC4172

• This study identified a major myelin protein in zebrafish, 36K, as a member of the SDR superfamily; an expression pattern similar to other myelin genes was demonstrated [9].

Associations of MGC4172 with chemical compounds

• The short-chain dehydrogenase reductase (SDR) family includes these steroid dehydrogenase enzymes and more than 60 other proteins from human, mammalian, insect, and bacterial sources [11].
• The d-aldohexose dehydrogenase from the thermoacidophilic archaea Thermoplasma acidophilum (AldT) belongs to the short-chain dehydrogenase/reductase (SDR) superfamily and catalyzes the oxidation of several monosaccharides with a preference for NAD(+) rather than NADP(+) as a cofactor [12].
• A putative catalytic triad consisting of tyrosine, serine, and lysine residues was identified in the ketoreductase (KR) domains of modular polyketide synthases (PKSs) based on homology modeling to the short chain dehydrogenase/reductase (SDR) superfamily of enzymes [13].
• Previously, two genes encoding retinol dehydrogenases (RoDH), which recognize holo-cellular retinol-binding protein as substrate, had been cloned, expressed and identified as members of the short-chain dehydrogenase/reductase (SDR) gene family [10].
• This enzyme is an interesting member of the NAD(P)H-dependent short-chain dehydrogenase/reductase (SDR) family of enzymes, being one of a pair of homologous dehydrogenases that act in concert in a single pathway to convert the R- and S-enantiomers of hydroxypropyl-coenzyme M to the achiral ketopropyl-coenzyme M product [14].

Other interactions of MGC4172

• We used affinity purification to identify a target of hydroxy-PP, carbonyl reductase 1 (CBR1), a short-chain dehydrogenase-reductase [15].

Analytical, diagnostic and therapeutic context of MGC4172

• Sequence alignment within SDR coupled with molecular modeling analysis has suggested that Gln-15, Asp-36, and Trp-37 of 15-PGDH may determine the coenzyme specificity of this enzyme [16].

References