1u7t
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(New page: 200px<br /> <applet load="1u7t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u7t, resolution 2.0Å" /> '''Crystal Structure of...)
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Revision as of 17:26, 12 November 2007
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Crystal Structure of ABAD/HSD10 with a Bound Inhibitor
Contents |
Overview
The enzyme 17beta-hydroxysteroid dehydrogenase type 10 (HSD10), also known, as amyloid beta-peptide-binding alcohol dehydrogenase (ABAD), has been, implicated in the development of Alzheimer's disease. This protein, a, member of the short-chain dehydrogenase/reductase family of enzymes, has, been shown to bind beta-amyloid and to participate in beta-amyloid, neurotoxicity. We have determined the crystal structure of human, ABAD/HSD10 complexed with NAD(+) and an inhibitory small molecule. The, inhibitor occupies the substrate-binding site and forms a covalent adduct, with the NAD(+) cofactor. The crystal structure provides a basis for the, design of potent, highly specific ABAD/HSD10 inhibitors with potential, application in the treatment of Alzheimer's disease.
Disease
Known diseases associated with this structure: 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency OMIM:[300256], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[601609], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[601609]
About this Structure
1U7T is a Single protein structure of sequence from Homo sapiens with TDT and NAD as ligands. Active as 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 Full crystallographic information is available from OCA.
Reference
Crystal structure of human ABAD/HSD10 with a bound inhibitor: implications for design of Alzheimer's disease therapeutics., Kissinger CR, Rejto PA, Pelletier LA, Thomson JA, Showalter RE, Abreo MA, Agree CS, Margosiak S, Meng JJ, Aust RM, Vanderpool D, Li B, Tempczyk-Russell A, Villafranca JE, J Mol Biol. 2004 Sep 17;342(3):943-52. PMID:15342248
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