ArticleProtein science : a publication of the Protein Society2000
Binding of Zn2+ to a Ca2+ loop allosterically attenuates the activity of factor VIIa and reduces its affinity for tissue factor.
Article in Protein science : a publication of the Protein Society, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Ginger phytochemical corona enhances hemocompatibility of metal oxide nanoparticles for blood-contacting applications.Scientific reports · 2026Article
- Strategies for Therapeutic Amelioration of Aberrant Plasma ZnInternational journal of molecular sciences · 2022Review
- Review
- Influence of zinc on glycosaminoglycan neutralisation during coagulation.Metallomics : integrated biometal science · 2018Review
- Structure-Function Relationship of the Interaction between Tissue Factor and Factor VIIa.Seminars in thrombosis and hemostasis · 2015Review
- Dietary zinc depletion and repletion affects plasma proteins: an analysis of the plasma proteome.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2013Article
- Structural biology of factor VIIa/tissue factor initiated coagulation.Frontiers in bioscience (Landmark edition) · 2012Review
- Review
- Zinc modulates the interaction of protein C and activated protein C with endothelial cell protein C receptor.The Journal of biological chemistry · 2010Article
- Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
- Ligand binding and allostery can emerge simultaneously.Protein science : a publication of the Protein Society · 2007Article
- Augmented intrinsic activity of Factor VIIa by replacement of residues 305, 314, 337 and 374: evidence of two unique mutational mechanisms of activity enhancement.The Biochemical journal · 2004Article
- Rational design of coagulation factor VIIa variants with substantially increased intrinsic activity.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
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5 authors at 1 institution in 1 country.
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Abstract
The protease domain of coagulation factor VIIa (FVIIa) is homologous to trypsin with a similar active site architecture. The catalytic function of FVIIa is regulated by allosteric modulations induced by binding of divalent metal ions and the cofactor tissue factor (TF). To further elucidate the mechanisms behind these transformations, the effects of Zn2+ binding to FVIIa in the free form and in complex with TF were investigated. Equilibrium dialysis suggested that two Zn2+ bind with high affinity to FVIIa outside the N-terminal gamma-carboxyglutamic acid (Gla) domain. Binding of Zn2+ to FVIIa, which was influenced by the presence of Ca2+, resulted in decreased amidolytic activity and slightly reduced affinity for TF. After binding to TF, FVIIa was less susceptible to zinc inhibition. Alanine substitutions for either of two histidine residues unique for FVIIa, His216, and His257, produced FVIIa variants with decreased sensitivity to Zn2+ inhibition. A search for putative Zn2+ binding sites in the crystal structure of the FVIIa protease domain was performed by Grid calculations. We identified a pair of Zn2+ binding sites in the Glu210-Glu220 Ca2+ binding loop adjacent to the so-called activation domain canonical to serine proteases. Based on our results, we propose a model that describes the conformational changes underlying the Zn2+-mediated allosteric down-regulation of FVIIa's activity.
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