High-resolution structure of the stable plasminogen activator inhibitor type-1 variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction studies and modeling.

Protein Science : a Publication of the Protein Society
Jan K Jensen, Peter G W Gettins

Abstract

Wild-type plasminogen activator inhibitor type-1 (PAI-1) rapidly converts to the inactive latent state under conditions of physiological pH and temperature. For in vivo studies of active PAI-1 in cell culture and in vivo model systems, the 14-1B PAI-1 mutant (N150H-K154T-Q319L-M354I), with its stabilized active conformation, has thus become the PAI-1 of choice. As a consequence of the increased stability, the only two forms likely to be encountered are the active or the cleaved form, the latter either free or complexed with target proteinase. We hereby report the first structure of the stable 14-1B PAI-1 variant in its reactive center cleaved form, to a resolution of 2.0 A. The >99% complete structure represents the highest resolved structure of free cleaved PAI-1. This high-resolution structure should be of great use for drug target development and for modeling protein-protein interactions such as those of PAI-1 with vitronectin.

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Citations

Jan 5, 2011·The Journal of Biological Chemistry·Zhonghui LinMingdong Huang
Jul 25, 2009·American Journal of Physiology. Renal Physiology·Yufeng HuangNancy A Noble
Apr 2, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jianyong ZhongJi Ma
Nov 12, 2014·TheScientificWorldJournal·Songul Yasar YildizMehmet Agirbasli
Oct 3, 2013·Thrombosis and Haemostasis·Tina M KoustedJan K Jensen
Feb 1, 2011·Protein Science : a Publication of the Protein Society·Lawrence C ThompsonCynthia B Peterson
Feb 1, 2011·Protein Science : a Publication of the Protein Society·Lawrence C ThompsonCynthia B Peterson
Jul 16, 2014·Critical Reviews in Biotechnology·F X Reymond SutandyChien-Sheng Chen
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Nov 4, 2015·Biological Chemistry·Jan PippelNorbert Sträter
Oct 1, 2020·International Journal of Molecular Sciences·Fasih Ahmad Rahman, Matthew Paul Krause
Dec 6, 2016·Acta Crystallographica. Section F, Structural Biology Communications·David A MeekinsKristin Michel
Jan 9, 2021·Frontiers in Cardiovascular Medicine·Machteld Sillen, Paul J Declerck
Apr 13, 2021·Biochemical Society Transactions·David J Wilkinson

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