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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

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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. / Jensen, Jan Kristian; Gettins, Peter G W.

I: Protein Science, Bind 17, Nr. 10, 01.10.2008, s. 1844-9.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{bf107643f73d4b14a0b965e9aec8e33a,
title = "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",
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.",
keywords = "Crystallization, Crystallography, X-Ray, Humans, Models, Molecular, Mutation, Plasminogen Activator Inhibitor 1, Protein Conformation, Protein Interaction Mapping, Protein Structure, Tertiary, Somatomedins",
author = "Jensen, {Jan Kristian} and Gettins, {Peter G W}",
year = "2008",
month = oct,
day = "1",
doi = "10.1110/ps.036707.108",
language = "English",
volume = "17",
pages = "1844--9",
journal = "Protein Science",
issn = "0961-8368",
publisher = "Wiley-Blackwell Publishing, Inc.",
number = "10",

}

RIS

TY - JOUR

T1 - 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

AU - Jensen, Jan Kristian

AU - Gettins, Peter G W

PY - 2008/10/1

Y1 - 2008/10/1

N2 - 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.

AB - 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.

KW - Crystallization

KW - Crystallography, X-Ray

KW - Humans

KW - Models, Molecular

KW - Mutation

KW - Plasminogen Activator Inhibitor 1

KW - Protein Conformation

KW - Protein Interaction Mapping

KW - Protein Structure, Tertiary

KW - Somatomedins

U2 - 10.1110/ps.036707.108

DO - 10.1110/ps.036707.108

M3 - Journal article

C2 - 18725454

VL - 17

SP - 1844

EP - 1849

JO - Protein Science

JF - Protein Science

SN - 0961-8368

IS - 10

ER -