Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q7LGC8 (HSD)
 3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

17 beta-hydroxysteroid dehydrogenases catalyze the oxidoreduction of hydroxy/oxo groups at position C17 of steroid hormones, thereby constituting a prereceptor control mechanism of hormone action. At present, 11 different mammalian 17 beta-hydroxysteroid dehydrogenases have been identified, catalyzing the cell- and steroid-specific activation and inactivation of estrogens and androgens. The human type 10 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD-10) is a multifunctional mitochondrial enzyme that efficiently catalyzes the oxidative inactivation at C17 of androgens and estrogens. However, it also mediates oxidation of 3 alpha-hydroxy groups of androgens, thereby reactivating androgen metabolites. Finally, it is involved in beta-oxidation of fatty acids by catalyzing the L-hydroxyacyl CoA dehydrogenase reaction of the beta-oxidation cycle. These features and expression profiles suggest a critical role of 17 beta-HSD-10 in neurodegenerative and steroid-dependent cancer forms. Since no three-dimensional structure of 17 beta-HSD-10 is available, homology modelling was carried out to understand the molecular basis of these substrate specificities. The structure obtained displays the properties of a one-domain, alpha/beta fold enzyme of the SDR family. The active site is located within a large, hydrophobic cleft, which forms optimal contacts with the different steroid surfaces. The data provide explanations for the substrate specificities toward the various classes of sex steroid hormones. The model is suitable to explore substrate and inhibitor characteristics that may be used in the development of novel strategies in the treatment of degenerative or malignant diseases.
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PMID:Human type 10 17 beta-hydroxysteroid dehydrogenase: molecular modelling and substrate docking. 1155 79

In late sepsis, it has been established that the liver plays a major role in the initiation of multiorgan failure, which is the most lethal complication in hospitals. The molecular mechanism underlying liver failure that results from sepsis remains elusive. This study was undertaken to identify the bona fide differentially expressed genes in the 18-h septic liver by suppression subtractive hybridization, and the data were corroborated by Northern blot analysis. The differential gene expression profile renders a clue as to the genes involved in septic liver failure. The cecal ligation and puncture (CLP) model of a polymicrobial septic rat was used, with the late sepsis referring to animals sacrificed at 18 h after CLP. We have identified three upregulated genes (TII-kininogen, serine protease inhibitor 2.2 [Spi2.2], and alpha 2 macroglobulin [alpha M]) and six down-regulated genes (hydroxysteroid dehydrogenase [3 alpha HSD], EST189895/mouse RNase4, bile acid-CoA-amino acid N-acyltransferase [kan-1/rBAT], IF1, albumin, and alpha 2u-globulins [alpha 2u-G PGCL1]). Among these genes, the 3 alpha HSD and kan-1/rBAT are involved in bile acid metabolism. The IF1 plays a crucial role in any disease that involves ATP hydrolysis by F1F0-ATPase. The alpha 2M, TII-kininogen, and Spi2.2 are protease inhibitors. The functions of the alpha 2u-G PGCL1 and EST189895/mouse RNase4 genes are unknown. The present results suggest that the roles of disturbance of bile acid metabolism/synthesis and the abolishment of ATP production may contribute to liver failure during late sepsis.
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PMID:Isolation of bona fide differentially expressed genes in the 18-hour sepsis liver by suppression subtractive hybridization. 1516 84

In this study, an artificial hydrolase was developed by combining the catalytic Ser/His/Asp triad with N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF), followed by coassembly of the peptides into nanofibers (CoA-HSD). The peptide-based nanofibers provide an ideal supramolecular framework to support the functional groups. Compared with the self-assembled catalytic nanofibers (SA-H), which contain only the catalytic histidine residue, the highest activity of CoA-HSD occurs when histidine, serine, and aspartate residues are at a ratio of 40:1:1. This indicates that the well-ordered nanofiber structure and the synergistic effects of serine and aspartate residues contribute to the enhancement in activity. Additionally, for the first time, molecular imprinting was applied to further enhance the activity of the peptide-based artificial enzyme (CoA-HSD). p-NPA was used as the molecular template to arrange the catalytic Ser/His/Asp triad residues in the proper orientation. As a result, the activity of imprinted coassembled CoA-HSD nanofibers is 7.86 times greater than that of nonimprinted CoA-HSD and 13.48 times that of SA-H.
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PMID:Enhancing the Activity of Peptide-Based Artificial Hydrolase with Catalytic Ser/His/Asp Triad and Molecular Imprinting. 2719 81