1DVN

LATENT FORM OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)

1DVN の概要

• エントリーDOI: 10.2210/pdb1dvn/pdb
• 関連するPDBエントリー: 1DVM
• 分子名称: PLASMINOGEN ACTIVATOR INHIBITOR-1 (2 entities in total)
• 機能のキーワード: serpin, pai-1, inhibitor, blood clotting
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P05121
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42819.07

構造登録者

Stout, T.J.,Graham, H.,Buckley, D.I.,Matthews, D.J. (登録日: 2000-01-21, 公開日: 2000-09-13, 最終更新日: 2024-02-07)

主引用文献

Stout, T.J.,Graham, H.,Buckley, D.I.,Matthews, D.J.
Structures of active and latent PAI-1: a possible stabilizing role for chloride ions.
Biochemistry, 39:8460-8469, 2000

PubMed Abstract: Serpins exhibit a range of physiological roles and can contribute to certain disease states dependent on their various conformations. Understanding the mechanisms of the large-scale conformational reorganizations of serpins may lead to a better understanding of their roles in various cardiovascular diseases. We have studied the serpin, plasminogen activator inhibitor 1 (PAI-1), in both the active and the latent state and found that anionic halide ions may play a role in the active-to-latent structural transition. Crystallographic analysis of a stable mutant form of active PAI-1 identified an anion-binding site between the central beta-sheet and a small surface domain. A chloride ion was modeled in this site, and its identity was confirmed by soaking crystals in a bromide-containing solution and calculating a crystallographic difference map. The anion thus located forms a 4-fold ligated linchpin that tethers the surface domain to the central beta-sheet into which the reactive center loop must insert during the active-to-latent transition. Timecourse experiments measuring active PAI-1 stability in the presence of various halide ions showed a clear trend for stabilization of the active form with F(-) > Cl(-) > Br(-) >> I(-). We propose that the "stickiness" of this pin (i.e., the electronegativity of the anion) contributes to the energetics of the active-to-latent transition in the PAI-1 serpin.

PubMed: 10913251
DOI: 10.1021/bi000290w

実験手法

X-RAY DIFFRACTION (2.1 Å)