1u7t
From Proteopedia
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|PDB= 1u7t |SIZE=350|CAPTION= <scene name='initialview01'>1u7t</scene>, resolution 2.0Å | |PDB= 1u7t |SIZE=350|CAPTION= <scene name='initialview01'>1u7t</scene>, resolution 2.0Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=TDT:1-AZEPAN-1-YL-2-PHENYL-2-(4-THIOXO-1,4-DIHYDRO-PYRAZOLO[3,4-D]PYRIMIDIN-5-YL)ETHANONE+ADDUCT'>TDT</scene> | + | |LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=TDT:1-AZEPAN-1-YL-2-PHENYL-2-(4-THIOXO-1,4-DIHYDRO-PYRAZOLO[3,4-D]PYRIMIDIN-5-YL)ETHANONE+ADDUCT'>TDT</scene> |
| - | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] </span> | |
|GENE= HADH2, ERAB, XH98G2, SCHAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HADH2, ERAB, XH98G2, SCHAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u7t OCA], [http://www.ebi.ac.uk/pdbsum/1u7t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1u7t RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300256 300256]], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Showalter, R E.]] | [[Category: Showalter, R E.]] | ||
[[Category: Villafranca, J E.]] | [[Category: Villafranca, J E.]] | ||
| - | [[Category: NAD]] | ||
| - | [[Category: TDT]] | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:06:32 2008'' |
Revision as of 21:06, 30 March 2008
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| , resolution 2.0Å | |||||||
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| Ligands: | , | ||||||
| Gene: | HADH2, ERAB, XH98G2, SCHAD (Homo sapiens) | ||||||
| Activity: | 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of ABAD/HSD10 with a Bound Inhibitor
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.
About this Structure
1U7T is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Mon Mar 31 00:06:32 2008
