1bkc: Difference between revisions
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[[Image:1bkc.gif|left|200px]] | [[Image:1bkc.gif|left|200px]] | ||
'''CATALYTIC DOMAIN OF TNF-ALPHA CONVERTING ENZYME (TACE)''' | {{Structure | ||
|PDB= 1bkc |SIZE=350|CAPTION= <scene name='initialview01'>1bkc</scene>, resolution 2.0Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=INN:3,N(D,L-[2-(HYDROXYAMINO-CARBONYL)METHYL]-4-METHYL PENTANOYL)L-3-(TERT-BUTYL)GLYCYL-L-ALANINE'>INN</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''CATALYTIC DOMAIN OF TNF-ALPHA CONVERTING ENZYME (TACE)''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1BKC is a [ | 1BKC is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BKC OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme., Maskos K, Fernandez-Catalan C, Huber R, Bourenkov GP, Bartunik H, Ellestad GA, Reddy P, Wolfson MF, Rauch CT, Castner BJ, Davis R, Clarke HR, Petersen M, Fitzner JN, Cerretti DP, March CJ, Paxton RJ, Black RA, Bode W, Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3408-12. PMID:[http:// | Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme., Maskos K, Fernandez-Catalan C, Huber R, Bourenkov GP, Bartunik H, Ellestad GA, Reddy P, Wolfson MF, Rauch CT, Castner BJ, Davis R, Clarke HR, Petersen M, Fitzner JN, Cerretti DP, March CJ, Paxton RJ, Black RA, Bode W, Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3408-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9520379 9520379] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: zn-endopeptidase]] | [[Category: zn-endopeptidase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:12:13 2008'' | ||
Revision as of 11:12, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
CATALYTIC DOMAIN OF TNF-ALPHA CONVERTING ENZYME (TACE)
OverviewOverview
Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective inflammatory reactions and kills tumor cells but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha is released from its membrane-bound precursor by a membrane-anchored proteinase, recently identified as a multidomain metalloproteinase called TNFalpha-converting enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This structure reveals a polypeptide fold and a catalytic zinc environment resembling that of the snake venom metalloproteinases, identifying TACE as a member of the adamalysin/ADAM family. However, a number of large insertion loops generate unique surface features. The pro-TNFalpha cleavage site fits to the active site of TACE but seems also to be determined by its position relative to the base of the compact trimeric TNFalpha cone. The active-site cleft of TACE shares properties with the matrix metalloproteinases but exhibits unique features such as a deep S3' pocket merging with the S1' specificity pocket below the surface. The structure thus opens a different approach toward the design of specific synthetic TACE inhibitors, which could act as effective therapeutic agents in vivo to modulate TNFalpha-induced pathophysiological effects, and might also help to control related shedding processes.
About this StructureAbout this Structure
1BKC is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme., Maskos K, Fernandez-Catalan C, Huber R, Bourenkov GP, Bartunik H, Ellestad GA, Reddy P, Wolfson MF, Rauch CT, Castner BJ, Davis R, Clarke HR, Petersen M, Fitzner JN, Cerretti DP, March CJ, Paxton RJ, Black RA, Bode W, Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3408-12. PMID:9520379
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