2D26

Active site distortion is sufficient for proteinase inhibit second crystal structure of covalent serpin-proteinase complex

2D26 の概要

• エントリーDOI: 10.2210/pdb2d26/pdb
• 分子名称: Alpha-1-antitrypsin, Elastase-1, ... (4 entities in total)
• 機能のキーワード: serpine proteinase, serpin, covalent serpin-proteinase comp protein-protein interactions, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted. Short peptide from AAT: Secreted, extracellular space, extracellular matrix: P01009 P01009; Secreted: P00772
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 70178.27

構造登録者

Dementiev, A.,Dobo, J.,Gettins, P.G. (登録日: 2005-09-03, 公開日: 2005-11-29, 最終更新日: 2024-10-23)

主引用文献

Dementiev, A.,Dobo, J.,Gettins, P.G.
Active Site Distortion Is Sufficient for Proteinase Inhibition by Serpins: Structure of the covalent complex of alpha 1-proteinase inhibitor with porcine pancreatic elastase
J.Biol.Chem., 281:3452-3457, 2006

PubMed Abstract: We report here the x-ray structure of a covalent serpin-proteinase complex, alpha1-proteinase inhibitor (alpha1PI) with porcine pancreatic elastase (PPE), which differs from the only other x-ray structure of such a complex, that of alpha1PI with trypsin, in showing nearly complete definition of the proteinase. alpha1PI complexes with trypsin, PPE, and human neutrophil elastase (HNE) showed similar rates of deacylation and enhanced susceptibility to proteolysis by exogenous proteinases in solution. The differences between the two x-ray structures therefore cannot arise from intrinsic differences in the inhibition mechanism. However, self-proteolysis of purified complex resulted in rapid cleavage of the trypsin complex, slower cleavage of the PPE complex, and only minimal cleavage of the HNE complex. This suggests that the earlier alpha1 PI-trypsin complex may have been proteolyzed and that the present structure is more likely to be representative of serpin-proteinase complexes. The present structure shows that active site distortion alone is sufficient for inhibition and suggests that enhanced proteolysis is not necessarily exploited in vivo.

PubMed: 16321984
DOI: 10.1074/jbc.M510564200

実験手法

X-RAY DIFFRACTION (3.3 Å)