1U7T

Crystal Structure of ABAD/HSD10 with a Bound Inhibitor

Summary for 1U7T

• Entry DOI: 10.2210/pdb1u7t/pdb
• Descriptor: 3-hydroxyacyl-CoA dehydrogenase type II, 1-AZEPAN-1-YL-2-PHENYL-2-(4-THIOXO-1,4-DIHYDRO-PYRAZOLO[3,4-D]PYRIMIDIN-5-YL)ETHANONE ADDUCT, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: protein-inhibitor complex, rossmann fold, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion : Q99714
• Total number of polymer chains: 4
• Total formula weight: 111748.30

Authors

Kissinger, C.R.,Rejto, P.A.,Pelletier, L.A.,Showalter, R.E.,Villafranca, J.E. (deposition date: 2004-08-04, release date: 2004-10-05, Last modification date: 2024-04-03)

Primary citation

Kissinger, C.R.,Rejto, P.A.,Pelletier, L.A.,Thomson, J.A.,Showalter, R.E.,Abreo, M.A.,Agree, C.S.,Margosiak, S.,Meng, J.J.,Aust, R.M.,Vanderpool, D.,Li, B.,Tempczyk-Russell, A.,Villafranca, J.E.
Crystal structure of human ABAD/HSD10 with a bound inhibitor: implications for design of Alzheimer's disease therapeutics
J.Mol.Biol., 342:943-952, 2004

PubMed Abstract: 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.

PubMed: 15342248
DOI: 10.1016/j.jmb.2004.07.071

Experimental method

X-RAY DIFFRACTION (2 Å)