Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange. / Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H; Persson, Egon; Jensen, Ole; Stennicke, Henning R; Andersen, Mette.

In: Journal of Biological Chemistry, Vol. 281, No. 32, 2006, p. 23018-24.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rand, KD, Jørgensen, T, Olsen, OH, Persson, E, Jensen, O, Stennicke, HR & Andersen, M 2006, 'Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange', Journal of Biological Chemistry, vol. 281, no. 32, pp. 23018-24. https://doi.org/10.1074/jbc.M602968200

APA

Rand, K. D., Jørgensen, T., Olsen, O. H., Persson, E., Jensen, O., Stennicke, H. R., & Andersen, M. (2006). Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange. Journal of Biological Chemistry, 281(32), 23018-24. https://doi.org/10.1074/jbc.M602968200

Vancouver

Rand KD, Jørgensen T, Olsen OH, Persson E, Jensen O, Stennicke HR et al. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange. Journal of Biological Chemistry. 2006;281(32):23018-24. https://doi.org/10.1074/jbc.M602968200

Author

Rand, Kasper Dyrberg ; Jørgensen, Thomas ; Olsen, Ole H ; Persson, Egon ; Jensen, Ole ; Stennicke, Henning R ; Andersen, Mette. / Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 32. pp. 23018-24.

Bibtex

@article{504f66ad639b4d1da8a1d7b8ee8729af,
title = "Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange",
abstract = "Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics of distinct molecular states, namely zymogen FVII, endoproteolytically cleaved FVIIa, TF-bound zymogen FVII, TF-bound FVIIa, and FVIIa in complex with an active site inhibitor. The hydrogen exchange kinetics of zymogen FVII and FVIIa are identical indicating highly similar solution structures. However, upon tissue factor binding, FVIIa undergoes dramatic structural stabilization as indicated by decreased exchange rates localized throughout the protease domain and in distant parts of the light chain, spanning across 50A and revealing a concerted interplay between functional sites in FVIIa. The results provide novel insights into the cofactor-induced activation of this important protease and reveal the potential for allosteric regulation in the trypsin family of proteases.",
keywords = "Allosteric Site, Enzyme Activation, Enzyme Precursors, Factor VIIa, Humans, Hydrogen, Kinetics, Mass Spectrometry, Models, Molecular, Molecular Conformation, Peptide Hydrolases, Protein Structure, Tertiary, Recombinant Proteins, Trypsin",
author = "Rand, {Kasper Dyrberg} and Thomas J{\o}rgensen and Olsen, {Ole H} and Egon Persson and Ole Jensen and Stennicke, {Henning R} and Mette Andersen",
year = "2006",
doi = "10.1074/jbc.M602968200",
language = "English",
volume = "281",
pages = "23018--24",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "32",

}

RIS

TY - JOUR

T1 - Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

AU - Rand, Kasper Dyrberg

AU - Jørgensen, Thomas

AU - Olsen, Ole H

AU - Persson, Egon

AU - Jensen, Ole

AU - Stennicke, Henning R

AU - Andersen, Mette

PY - 2006

Y1 - 2006

N2 - Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics of distinct molecular states, namely zymogen FVII, endoproteolytically cleaved FVIIa, TF-bound zymogen FVII, TF-bound FVIIa, and FVIIa in complex with an active site inhibitor. The hydrogen exchange kinetics of zymogen FVII and FVIIa are identical indicating highly similar solution structures. However, upon tissue factor binding, FVIIa undergoes dramatic structural stabilization as indicated by decreased exchange rates localized throughout the protease domain and in distant parts of the light chain, spanning across 50A and revealing a concerted interplay between functional sites in FVIIa. The results provide novel insights into the cofactor-induced activation of this important protease and reveal the potential for allosteric regulation in the trypsin family of proteases.

AB - Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics of distinct molecular states, namely zymogen FVII, endoproteolytically cleaved FVIIa, TF-bound zymogen FVII, TF-bound FVIIa, and FVIIa in complex with an active site inhibitor. The hydrogen exchange kinetics of zymogen FVII and FVIIa are identical indicating highly similar solution structures. However, upon tissue factor binding, FVIIa undergoes dramatic structural stabilization as indicated by decreased exchange rates localized throughout the protease domain and in distant parts of the light chain, spanning across 50A and revealing a concerted interplay between functional sites in FVIIa. The results provide novel insights into the cofactor-induced activation of this important protease and reveal the potential for allosteric regulation in the trypsin family of proteases.

KW - Allosteric Site

KW - Enzyme Activation

KW - Enzyme Precursors

KW - Factor VIIa

KW - Humans

KW - Hydrogen

KW - Kinetics

KW - Mass Spectrometry

KW - Models, Molecular

KW - Molecular Conformation

KW - Peptide Hydrolases

KW - Protein Structure, Tertiary

KW - Recombinant Proteins

KW - Trypsin

U2 - 10.1074/jbc.M602968200

DO - 10.1074/jbc.M602968200

M3 - Journal article

C2 - 16687401

VL - 281

SP - 23018

EP - 23024

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 32

ER -

ID: 40130010