1CEW

THE 2.0 ANGSTROMS X-RAY CRYSTAL STRUCTURE OF CHICKEN EGG WHITE CYSTATIN AND ITS POSSIBLE MODE OF INTERACTION WITH CYSTEINE PROTEINASES

1CEW の概要

• エントリーDOI: 10.2210/pdb1cew/pdb
• 分子名称: CYSTATIN (2 entities in total)
• 機能のキーワード: proteinase inhibitor(cysteine)
• 由来する生物種: Gallus gallus (chicken)
• 細胞内の位置: Secreted: P01038
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12204.87

構造登録者

Bode, W.,Musil, D.,Huber, R. (登録日: 1993-04-21, 公開日: 1994-01-31, 最終更新日: 2024-10-16)

主引用文献

Bode, W.,Engh, R.,Musil, D.,Thiele, U.,Huber, R.,Karshikov, A.,Brzin, J.,Kos, J.,Turk, V.
The 2.0 A X-ray crystal structure of chicken egg white cystatin and its possible mode of interaction with cysteine proteinases.
EMBO J., 7:2593-2599, 1988

PubMed Abstract: The crystal structure of chicken egg white cystatin has been solved by X-ray diffraction methods using the multiple isomorphous replacement technique. Its structure has been refined to a crystallographic R value of 0.19 using X-ray data between 6 and 2.0A. The molecule consists mainly of a straight five-turn alpha-helix, a five-stranded antiparallel beta-pleated sheet which is twisted and wrapped around the alpha-helix and an appending segment of partially alpha-helical geometry. The 'highly conserved' region from Gln53I to Gly57I implicated with binding to cysteine proteinases folds into a tight beta-hairpin loop which on opposite sides is flanked by the amino-terminal segment and by a second hairpin loop made up of the similarly conserved segment Pro103I - Trp104I. These loops and the amino-terminal Gly9I - Ala10I form a wedge-shaped 'edge' which is quite complementary to the 'active site cleft' of papain. Docking experiments suggest a unique model for the interaction of cystatin and papain: according to it both hairpin loops of cystatin make major binding interactions with the highly conserved residues Gly23, Gln19, Trp177 and Ala136 of papain in the neighbourhood of the reactive site Cys25; the amino-terminal segment Gly9I - Ala10I of bound cystatin is directed towards the substrate subsite S2, but in an inappropriate conformation and too far away to be attacked by the reactive site Cys25. As a consequence, the mechanism of the interaction between cysteine proteinases and their cystatin-like inhibitors seems to be fundamentally different from the 'standard mechanism' defined for serine proteinases and most of their protein inhibitors.

PubMed: 3191914

実験手法

X-RAY DIFFRACTION (2 Å)