2a8h | pdb_00002a8h

Crystal structure of catalytic domain of TACE with Thiomorpholine Sulfonamide Hydroxamate inhibitor

spinqualitylabelsall models 2a8h, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2a8h is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 4NH, ZN Related: 1bkc, 1zxc Gene: ADAM17, CSVP, TACE (HUMAN) Activity: ADAM 17 endopeptidase, with EC number 3.4.24.86 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [ADA17_HUMAN] Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:614328]. NISBD is a disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized. Function [ADA17_HUMAN] Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Also involved in the activation of Notch pathway (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA. Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.,Levin JI, Chen JM, Laakso LM, Du M, Schmid J, Xu W, Cummons T, Xu J, Jin G, Barone D, Skotnicki JS Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. Epub 2006 Jan 19. PMID:16426848 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also A Disintegrin And Metalloproteinase

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