1DB2

CRYSTAL STRUCTURE OF NATIVE PLASMINOGEN ACTIVATOR INHIBITOR-1

1DB2 の概要

• エントリーDOI: 10.2210/pdb1db2/pdb
• 関連するPDBエントリー: 1A7C 9PAI
• 分子名称: PLASMINOGEN ACTIVATOR INHIBITOR-1 (1 entity in total)
• 機能のキーワード: native serpin, hydrolase inhibitor
• 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: 2
• 化学式量合計: 85027.48

構造登録者

Nar, H.,Bauer, M.,Stassen, J.M.,Lang, D.,Gils, A.,Declerck, P. (登録日: 1999-11-02, 公開日: 1999-11-10, 最終更新日: 2024-02-07)

主引用文献

Nar, H.,Bauer, M.,Stassen, J.M.,Lang, D.,Gils, A.,Declerck, P.J.
Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation.
J.Mol.Biol., 297:683-695, 2000

PubMed Abstract: The crystal structure of a constitutively active multiple site mutant of plasminogen activator inhibitor 1 (PAI-1) was determined and refined at a resolution of 2.7 A. The present structure comprises a dimer of two crystallographically independent PAI-1 molecules that pack by association of the residues P6 to P3 of the reactive centre loop of one molecule (A) with the edge of the main beta-sheet A of the other molecule (B).Thus, the reactive centre loop is ordered for molecule A by crystal packing forces, while for molecule B it is unconstrained by crystal packing contacts and is disordered. The overall structure of active PAI-1 is similar to the structures of other active inhibitory serpins exhibiting as the major secondary structural feature a five-stranded beta-sheet A and an intact proteinase-binding loop protruding from the one end of the elongated molecule. No preinsertion of the reactive centre loop is observed in this structure.A comparison of the present structure with the previously determined crystal structures of PAI-1 in its alternative conformations reveals that, upon cleavage of an intact form of PAI-1 or formation of latent PAI-1, the well-characterised rearrangements of the serpin secondary structural elements are accompanied by dramatic and partly unexpected conformational changes of helical and loop structures proximal to beta-sheet A. The present structure explains the stabilising effects of the mutated residues, reveals the structural cause for the observed spectroscopic differences between active and latent PAI-1, and provides new insights into possible mechanisms of stabilisation by its natural binding partner, vitronectin.

PubMed: 10731421
DOI: 10.1006/jmbi.2000.3604

実験手法

X-RAY DIFFRACTION (2.7 Å)