1NB5

Crystal structure of stefin A in complex with cathepsin H

1NB5 の概要

• エントリーDOI: 10.2210/pdb1nb5/pdb
• 関連するPDBエントリー: 1NB3
• 分子名称: Cathepsin H, Cathepsin H MINI CHAIN, STEFIN A, ... (4 entities in total)
• 機能のキーワード: cysteine proteinase, aminopeptidase, cystatin, enzyme-inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 147137.62

構造登録者

Jenko, S.,Dolenc, I.,Guncar, G.,Dobersek, A.,Podobnik, M.,Turk, D. (登録日: 2002-12-02, 公開日: 2003-02-18, 最終更新日: 2024-10-16)

主引用文献

Jenko, S.,Dolenc, I.,Guncar, G.,Dobersek, A.,Podobnik, M.,Turk, D.
Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases
J.Mol.Biol., 326:875-885, 2003

PubMed Abstract: Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be explained by the stefin B-papain complex. The crystal structure of human stefin A bound to an aminopeptidase, porcine cathepsin H, has been determined in monoclinic and orthorhombic crystal forms at 2.8A and 2.4A resolutions, respectively. The asymmetric unit of each form contains four complexes. The structures are similar to the stefin B-papain complex, but with a few distinct differences. On binding, the N-terminal residues of stefin A adopt the form of a hook, which pushes away cathepsin H mini-chain residues and distorts the structure of the short four residue insertion (Lys155A-Asp155D) unique to cathepsin H. Comparison with the structure of isolated cathepsin H shows that the rims of the cathepsin H structure are slightly displaced (up to 1A) from their position in the free enzyme. Furthermore, comparison with the stefin B-papain complex showed that molecules of stefin A bind about 0.8A deeper into the active site cleft of cathepsin H than stefin B into papain. The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex. Carboxymethylation of papain seems to have prevented the formation of the genuine binding geometry between a papain-like enzyme and a cystatin-type inhibitor as we observe it in the structure presented here.

PubMed: 12581647
DOI: 10.1016/S0022-2836(02)01432-8

実験手法

X-RAY DIFFRACTION (2.4 Å)