3kme
Crystal structure of catalytic domain of TACE with phenyl-pyrrolidinyl-tartrate inhibitorCrystal structure of catalytic domain of TACE with phenyl-pyrrolidinyl-tartrate inhibitor
Template:ABSTRACT PUBMED 20022498
DiseaseDisease
[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.[1]
FunctionFunction
[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).[2][3]
About this StructureAbout this Structure
3kme is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Rosner KE, Guo Z, Orth P, Shipps GW Jr, Belanger DB, Chan TY, Curran PJ, Dai C, Deng Y, Girijavallabhan VM, Hong L, Lavey BJ, Lee JF, Li D, Liu Z, Popovici-Muller J, Ting PC, Vaccaro H, Wang L, Wang T, Yu W, Zhou G, Niu X, Sun J, Kozlowski JA, Lundell DJ, Madison V, McKittrick B, Piwinski JJ, Shih NY, Arshad Siddiqui M, Strickland CO. The discovery of novel tartrate-based TNF-alpha converting enzyme (TACE) inhibitors. Bioorg Med Chem Lett. 2010 Feb 1;20(3):1189-93. Epub 2009 Dec 5. PMID:20022498 doi:10.1016/j.bmcl.2009.12.004
- ↑ Blaydon DC, Biancheri P, Di WL, Plagnol V, Cabral RM, Brooke MA, van Heel DA, Ruschendorf F, Toynbee M, Walne A, O'Toole EA, Martin JE, Lindley K, Vulliamy T, Abrams DJ, MacDonald TT, Harper JI, Kelsell DP. Inflammatory skin and bowel disease linked to ADAM17 deletion. N Engl J Med. 2011 Oct 20;365(16):1502-8. doi: 10.1056/NEJMoa1100721. PMID:22010916 doi:10.1056/NEJMoa1100721
- ↑ Thathiah A, Blobel CP, Carson DD. Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding. J Biol Chem. 2003 Jan 31;278(5):3386-94. Epub 2002 Nov 18. PMID:12441351 doi:10.1074/jbc.M208326200
- ↑ Rabquer BJ, Amin MA, Teegala N, Shaheen MK, Tsou PS, Ruth JH, Lesch CA, Imhof BA, Koch AE. Junctional adhesion molecule-C is a soluble mediator of angiogenesis. J Immunol. 2010 Aug 1;185(3):1777-85. doi: 10.4049/jimmunol.1000556. Epub 2010, Jun 30. PMID:20592283 doi:10.4049/jimmunol.1000556
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- ADAM 17 endopeptidase
- Homo sapiens
- Orth, P.
- A disintegrin and metalloproteinase domain 17
- Cleavage on pair of basic residue
- Glycoprotein
- Hydrolase
- Membrane
- Metal-binding
- Metalloprotease
- Notch signaling pathway
- Phosphoprotein
- Protease
- Snake venom-like protease
- Tnf-alpha convertase
- Tnf-alpha-converting enzyme
- Zymogen