1IZ2

Interactions causing the kinetic trap in serpin protein folding

1IZ2 の概要

• エントリーDOI: 10.2210/pdb1iz2/pdb
• 分子名称: alpha1-antitrypsin, alpha-D-glucopyranose-(1-2)-(5R)-5-[(2R)-2-hydroxynonyl]-beta-D-xylulofuranose (3 entities in total)
• 機能のキーワード: serpin, folding, antitrypsin, protein binding
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44657.63

構造登録者

Im, H.,Woo, M.-S.,Hwang, K.Y.,Yu, M.-H. (登録日: 2002-09-19, 公開日: 2003-02-11, 最終更新日: 2023-12-27)

主引用文献

Im, H.,Woo, M.-S.,Hwang, K.Y.,Yu, M.-H.
Interactions causing the kinetic trap in serpin protein folding
J.BIOL.CHEM., 277:46347-46354, 2002

PubMed Abstract: Conformational transition is fundamental to the mechanism of functional regulation in proteins, and serpins (serine protease inhibitors) can provide insight into this process. Serpins are metastable in their native forms, and they ordinarily undergo conformational transition to a stable state only when they form a tight complex with target proteases. The metastable native form is thus considered to be a kinetically trapped folding intermediate. We sought to understand the nature of the serpin kinetic trap as a step toward discovering how conformational transition is regulated. We found that mutations of the B/C beta-barrel of native alpha(1)-antitrypsin, a prototypical serpin, allowed conversion of the molecule into a more stable state. A 2.2 A resolution crystal structure of the stable form (PDB code, ) showed that the reactive site loop is inserted into an A beta-sheet, as in the latent plasminogen activator inhibitor-1. Mutational analyses suggest strongly that interactions not found in the final stable form cause the kinetic trap in serpin protein folding.

PubMed: 12244055
DOI: 10.1074/jbc.M207682200

実験手法

X-RAY DIFFRACTION (2.2 Å)