3edz | pdb_00003edz

Crystal structure of catalytic domain of TACE with hydroxamate inhibitor

spinqualitylabelsall models 3edz, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3edz is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 550, CIT, INN, ZN Related: 1bkc, 2fv9, 2fv5 Gene: ADAM17, CSVP, TACE (Homo sapiens) Activity: ADAM 17 endopeptidase, with EC number 3.4.24.86 Resources: FirstGlance, OCA, 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 cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1'-S3' pocket. Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.,Mazzola RD Jr, Zhu Z, Sinning L, McKittrick B, Lavey B, Spitler J, Kozlowski J, Neng-Yang S, Zhou G, Guo Z, Orth P, Madison V, Sun J, Lundell D, Niu X Bioorg Med Chem Lett. 2008 Nov 1;18(21):5809-14. Epub 2008 Sep 13. PMID:18835710 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also A Disintegrin And Metalloproteinase

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