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Rezymogenation of active urokinase induced by an inhibitory antibody

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Standard

Rezymogenation of active urokinase induced by an inhibitory antibody. / Jiang, Longguang; Botkjaer, Kenneth A; Andersen, Lisbeth M; Yuan, Cai; Andreasen, Peter; Huang, Mingdong.

I: Biochemical Journal, Bind 449, Nr. 1, 01.2013, s. 161-166.

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

Harvard

Jiang, L, Botkjaer, KA, Andersen, LM, Yuan, C, Andreasen, P & Huang, M 2013, 'Rezymogenation of active urokinase induced by an inhibitory antibody', Biochemical Journal, bind 449, nr. 1, s. 161-166. https://doi.org/10.1042/BJ20121132

APA

Jiang, L., Botkjaer, K. A., Andersen, L. M., Yuan, C., Andreasen, P., & Huang, M. (2013). Rezymogenation of active urokinase induced by an inhibitory antibody. Biochemical Journal, 449(1), 161-166. https://doi.org/10.1042/BJ20121132

CBE

Jiang L, Botkjaer KA, Andersen LM, Yuan C, Andreasen P, Huang M. 2013. Rezymogenation of active urokinase induced by an inhibitory antibody. Biochemical Journal. 449(1):161-166. https://doi.org/10.1042/BJ20121132

MLA

Vancouver

Jiang L, Botkjaer KA, Andersen LM, Yuan C, Andreasen P, Huang M. Rezymogenation of active urokinase induced by an inhibitory antibody. Biochemical Journal. 2013 jan;449(1):161-166. https://doi.org/10.1042/BJ20121132

Author

Jiang, Longguang ; Botkjaer, Kenneth A ; Andersen, Lisbeth M ; Yuan, Cai ; Andreasen, Peter ; Huang, Mingdong. / Rezymogenation of active urokinase induced by an inhibitory antibody. I: Biochemical Journal. 2013 ; Bind 449, Nr. 1. s. 161-166.

Bibtex

@article{f7f489d0cbd842f4ab00f3a791299434,
title = "Rezymogenation of active urokinase induced by an inhibitory antibody",
abstract = "An important regulatory mechanism of serine proteases is the proteolytic conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This activation process is generally considered an irreversible process. In the present study, we demonstrate that an active enzyme can be converted back into its zymogen form. We determined the crystal structure of uPA (urokinase-type plasminogen activator) in complex with an inhibitory antibody, revealing that the antibody 'rezymogenizes' already activated uPA. The present study demonstrates a new regulatory mechanism of protease activity, which is also an extreme case of protein allostery. Mechanistically, the antibody binds a single surface-exposed loop, named the autolysis loop, thereby preventing the stabilization of uPA in its active conformation. We argue that this autolysis loop is a key structural element for rezymogenation of other proteases, and will be a new target site for pharmacological intervention with serine protease activity.",
keywords = "Crystallography; acncer; serine proteases, antibody, autolysis loop, crystal structure, protease, urokinase, zymogen",
author = "Longguang Jiang and Botkjaer, {Kenneth A} and Andersen, {Lisbeth M} and Cai Yuan and Peter Andreasen and Mingdong Huang",
year = "2013",
month = jan,
doi = "10.1042/BJ20121132",
language = "English",
volume = "449",
pages = "161--166",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Rezymogenation of active urokinase induced by an inhibitory antibody

AU - Jiang, Longguang

AU - Botkjaer, Kenneth A

AU - Andersen, Lisbeth M

AU - Yuan, Cai

AU - Andreasen, Peter

AU - Huang, Mingdong

PY - 2013/1

Y1 - 2013/1

N2 - An important regulatory mechanism of serine proteases is the proteolytic conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This activation process is generally considered an irreversible process. In the present study, we demonstrate that an active enzyme can be converted back into its zymogen form. We determined the crystal structure of uPA (urokinase-type plasminogen activator) in complex with an inhibitory antibody, revealing that the antibody 'rezymogenizes' already activated uPA. The present study demonstrates a new regulatory mechanism of protease activity, which is also an extreme case of protein allostery. Mechanistically, the antibody binds a single surface-exposed loop, named the autolysis loop, thereby preventing the stabilization of uPA in its active conformation. We argue that this autolysis loop is a key structural element for rezymogenation of other proteases, and will be a new target site for pharmacological intervention with serine protease activity.

AB - An important regulatory mechanism of serine proteases is the proteolytic conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This activation process is generally considered an irreversible process. In the present study, we demonstrate that an active enzyme can be converted back into its zymogen form. We determined the crystal structure of uPA (urokinase-type plasminogen activator) in complex with an inhibitory antibody, revealing that the antibody 'rezymogenizes' already activated uPA. The present study demonstrates a new regulatory mechanism of protease activity, which is also an extreme case of protein allostery. Mechanistically, the antibody binds a single surface-exposed loop, named the autolysis loop, thereby preventing the stabilization of uPA in its active conformation. We argue that this autolysis loop is a key structural element for rezymogenation of other proteases, and will be a new target site for pharmacological intervention with serine protease activity.

KW - Crystallography; acncer; serine proteases

KW - antibody

KW - autolysis loop

KW - crystal structure

KW - protease

KW - urokinase

KW - zymogen

U2 - 10.1042/BJ20121132

DO - 10.1042/BJ20121132

M3 - Journal article

C2 - 23016918

VL - 449

SP - 161

EP - 166

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

ER -