1BKC

CATALYTIC DOMAIN OF TNF-ALPHA CONVERTING ENZYME (TACE)

1BKC の概要

• エントリーDOI: 10.2210/pdb1bkc/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000919
• 分子名称: TUMOR NECROSIS FACTOR-ALPHA-CONVERTING ENZYME, ZINC ION, N-{(2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl}-3-methyl-L-valyl-N-(2-aminoethyl)-L-alaninamide, ... (6 entities in total)
• 機能のキーワード: zn-endopeptidase, hydrolase, tnf-alpha
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P78536 P78536 P78536
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117771.63

構造登録者

Maskos, K.,Fernandez-Catalan, C.,Bode, W. (登録日: 1998-04-23, 公開日: 1999-06-22, 最終更新日: 2024-11-06)

主引用文献

Maskos, K.,Fernandez-Catalan, C.,Huber, R.,Bourenkov, G.P.,Bartunik, H.,Ellestad, G.A.,Reddy, P.,Wolfson, M.F.,Rauch, C.T.,Castner, B.J.,Davis, R.,Clarke, H.R.,Petersen, M.,Fitzner, J.N.,Cerretti, D.P.,March, C.J.,Paxton, R.J.,Black, R.A.,Bode, W.
Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme.
Proc.Natl.Acad.Sci.USA, 95:3408-3412, 1998

PubMed Abstract: 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.

PubMed: 9520379
DOI: 10.1073/pnas.95.7.3408

実験手法

X-RAY DIFFRACTION (2 Å)