3AIG

ADAMALYSIN II WITH PEPTIDOMIMETIC INHIBITOR POL656

3AIG の概要

• エントリーDOI: 10.2210/pdb3aig/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000372
• 分子名称: ADAMALYSIN II, ZINC ION, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: snake venom metalloendopetidase, zinc protease, metalloprotease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Crotalus adamanteus (eastern diamondback rattlesnake)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23777.50

構造登録者

Gomis-Rueth, F.X.,Meyer, E.F.,Kress, L.F.,Politi, V. (登録日: 1997-10-12, 公開日: 1998-04-15, 最終更新日: 2024-11-20)

主引用文献

Gomis-Ruth, F.X.,Meyer, E.F.,Kress, L.F.,Politi, V.
Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.
Protein Sci., 7:283-292, 1998

PubMed Abstract: Crotalus adamanteus snake venom adamalysin II is the structural prototype of the adamalysin or ADAM family comprising proteolytic domains of snake venom metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor necrosis factor alpha convertase, TACE, involved in the release of the inflammatory cytokine, TNFalpha. The structure of adamalysin II in noncovalent complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol 647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.8 A resolution. The inhibitors bind to the S'-side of the proteinase, inserting between two protein segments, establishing a mixed parallel-antiparallel three-stranded beta-sheet and coordinate the central zinc ion in a bidentate manner via their two C-terminal oxygen atoms. The proteinase-inhibitor complexes are described in detail and are compared with other known structures. An adamalysin-based model of the active site of TACE reveals that these small molecules would probably fit into the active site cleft of this latter metalloproteinase, providing a starting model for the rational design of TACE inhibitors.

PubMed: 9521103

実験手法

X-RAY DIFFRACTION (2.8 Å)