scholarly journals Assessment of the protein interaction between coagulation factor XII and corn trypsin inhibitor by molecular docking and biochemical validation

2017 ◽  
Vol 15 (9) ◽  
pp. 1818-1828 ◽  
Author(s):  
B. K. Hamad ◽  
M. Pathak ◽  
R. Manna ◽  
P. M. Fischer ◽  
J. Emsley ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Interaction ◽  
Trypsin Inhibitor ◽  
Coagulation Factor ◽  
Factor Xii ◽  
Biochemical Validation ◽  
Corn Trypsin Inhibitor

Assembly of High Molecular Weight Kininogen and Activation of Prekallikrein on Cell Matrix

2001 ◽  
Vol 86 (09) ◽  
pp. 840-847 ◽  
Author(s):  
Z. Shariat-Madar ◽  
F. Mahdi ◽  
C. A. M. Sampaio ◽  
A. H. Schmaier ◽  
G. Motta
Keyword(s):  
Molecular Weight ◽  
Endothelial Cells ◽  
High Molecular Weight ◽  
Trypsin Inhibitor ◽  
Umbilical Vein ◽  
Sodium Dodecyl ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Urokinase Plasminogen Activator Receptor ◽  
Corn Trypsin Inhibitor

SummaryInvestigations determined if extracellular matrix of endothelial cells (EC) is a platform for HK assembly and PK activation. In buffers containing bovine serum albumin, biotin-HK binding to ECV304 cells or their matrix requires ≥ 50 µM added Zn 2+. Ortho-phenanthroline or a HK domain 5 peptide blocks HK binding. Binding to umbilical vein EC or matrix, but not ECV304 cells or matrix, is mediated by cytokeratin 1. Biotin-HK binds to ECV304 cells or matrix with a Kd of 15.8 or 9.0 nM and a Bmax of 2.6 107 or 2.4 107 sites/cell, respectively. PK activation on ECV304 cells or matrix is blocked by antipain or SBTI and corn trypsin inhibitor partially inhibits kallikrein formation. PK activation occurs on ECV304 cells or matrix prepared without serum or in human factor XII deficient serum, indicating that the PK activator is not factor XIIa. EC matrix promotes plasminogen activation after the assembly of HK, PK and pro-urokinase. These studies indicate that matrix of various EC has the ability to assemble HK allowing for PK activation and subsequent activities.Abbreviations: EC: endothelial cells, FXII: factor XII, HK: high molecular weight kininogen, HKa: bradykinin-free HK, PK: plasma prekallikrein, Pro-UK: pro-urokinase, uPAR: urokinase plasminogen activator receptor, tcuPA: twochain urokinase, CK1: cytokeratin 1, SBTI: soybean trypsin inhibitor, HUVEC: human umbilical vein endothelial cell, SDS-PAGE: sodium dodecyl sulfatepolyacrylamide gel electrophoresis, CTI: corn trypsin inhibitor, p-APMSF: p-amidinophenylmethylsulfonylfluoride, EBSS: Earle’s Balanced Salt Solution

scholarly journals Diagnosis of hereditary Angioedema by genetic mutation of coagulation factor XII

2021 ◽  
Vol 147 (2) ◽  
pp. AB23
Author(s):  
Natasha Ferraroni ◽  
Gabriela Yoshimoto ◽  
Camila Veronez ◽  
Luiza Silva ◽  
Marina Batista ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Coagulation Factor ◽  
Genetic Mutation ◽  
Factor Xii

scholarly journals Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa.

1985 ◽  
Vol 260 (25) ◽  
pp. 13666-13676 ◽  
Author(s):  
D E Cool ◽  
C J Edgell ◽  
G V Louie ◽  
M J Zoller ◽  
G D Brayer ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Human Blood ◽  
Primary Structure ◽  
Tertiary Structure ◽  
Coagulation Factor ◽  
Factor Xii ◽  
Factor Xiia ◽  
Human Blood Coagulation

scholarly journals Studies on the Mechanism of Gegen Qinlian Decoction in Treating Diabetes Mellitus Based on Network Pharmacology

2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098213
Author(s):  
Xiaodong Deng ◽  
Yuhua Liang ◽  
Jianmei Hu ◽  
Yuhui Yang
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Network Pharmacology ◽  
Hub Genes ◽  
Topological Parameters

Diabetes mellitus (DM) is a chronic disease that is very common and seriously threatens patient health. Gegen Qinlian decoction (GQD) has long been applied clinically, but its mechanism in pharmacology has not been extensively and systematically studied. A GQD protein interaction network and diabetes protein interaction network were constructed based on the methods of system biology. Functional module analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Gene Ontology (GO) enrichment analysis were carried out on the 2 networks. The hub nodes were filtered by comparative analysis. The topological parameters, interactions, and biological functions of the 2 networks were analyzed in multiple ways. By applying GEO-based external datasets to verify the results of our analysis that the Gene Set Enrichment Analysis (GSEA) displayed metabolic pathways in which hub genes played roles in regulating different expression states. Molecular docking is used to verify the effective components that can be combined with hub nodes. By comparing the 2 networks, 24 hub targets were filtered. There were 7 complex relationships between the networks. The results showed 4 topological parameters of the 24 selected hub targets that were much higher than the median values, suggesting that these hub targets show specific involvement in the network. The hub genes were verified in the GEO database, and these genes were closely related to the biological processes involved in glucose metabolism. Molecular docking results showed that 5,7,2', 6'-tetrahydroxyflavone, magnograndiolide, gancaonin I, isoglycyrol, gancaonin A, worenine, and glyzaglabrin produced the strongest binding effect with 10 hub nodes. This compound–target mode of interaction may be the main mechanism of action of GQD. This study reflected the synergistic characteristics of multiple targets and multiple pathways of traditional Chinese medicine and discussed the mechanism of GQD in the treatment of DM at the molecular pharmacological level.

Fibrinolyse- und Thrombophilieparameter unter systemischer Prostaglandin E1-Therapie bei peripherer arterieller Verschlusskrankheit

VASA ◽  
2003 ◽  
Vol 32 (3) ◽  
pp. 145-148 ◽  
Author(s):  
Kuss ◽  
Heidrich ◽  
Koettgen
Keyword(s):  
Coagulation Factor ◽  
Plasminogen Activator Inhibitor ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Prostaglandin E ◽  
Factor Xii ◽  
Significant Difference ◽  
Peripheral Arterial ◽  
Fibrinolytic Capacity

Background: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). Patients and methods: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global®, plasminogen, plasminogen activator inhibitor activity (PAI), alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). Results: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global®, plasminogen, PAI, alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. Conclusion: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.

Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

2004 ◽  
Vol 92 (09) ◽  
pp. 503-508 ◽  
Author(s):  
Hans-Ulrich Pauer ◽  
Thomas Renné ◽  
Bernhard Hemmerlein ◽  
Tobias Legler ◽  
Saskia Fritzlar ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Mendelian Inheritance ◽  
Biological Role ◽  
Factor Xii ◽  
Wild Type ◽  
Contact Phase ◽  
Health And Disease

SummaryTo analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII-/-) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII,V, II and fibrinogen did not differ between FXII-/- mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore, matings of FXII-/- males and FXII-/females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII-/females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII-/mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII-/mice will be helpful to elucidate the biological role(s) of FXII in health and disease.

Structure of plasma and tissue kallikreins

2013 ◽  
Vol 110 (09) ◽  
pp. 423-433 ◽  
Author(s):  
Monika Pathak ◽  
Szu Shen Wong ◽  
Ingrid Dreveny ◽  
Jonas Emsley
Keyword(s):  
Molecular Weight ◽  
Serine Proteases ◽  
Molecular Mechanisms ◽  
Substrate Recognition ◽  
Coagulation Factor ◽  
Structural Data ◽  
Pressure Control ◽  
Factor Xii ◽  
Zymogen Activation ◽  
Kinin System

SummaryThe kallikrein kinin system (KKS) consists of serine proteases involved in the production of peptides called kinins, principally bradykinin and Lys-bradykinin (kallidin). The KKS contributes to a variety of physiological processes including inflammation, blood pressure control and coagulation. Here we review the protein structural data available for these serine proteases and examine the molecular mechanisms of zymogen activation and substrate recognition focusing on plasma kallikrein (PK) and tissue kallikrein (KLK1) cleavage of kininogens. PK circulates as a zymogen bound to high-molecular-weight kininogen (HK). PK is activated by coagulation factor XIIa and then cleaves HK to generate bradykinin and factor XII to generate further XIIa. A structure has been described for the activated PK protease domain in complex with the inhibitor benzamidine. Kallikrein-related peptidases (KLKs) have a distinct domain structure and exist as a family of 15 genes which are differentially expressed in many tissues and the central nervous system. They cleave a wide variety of substrates including low-molecular-weight kininogen (LK) and matrix proteins. Crystal structures are available for KLK1, 3, 4, 5, 6 and 7 activated protease domains typically in complex with S1 pocket inhibitors. A substrate mimetic complex is described for KLK3 which provides insight into substrate recognition. A zymogen crystal structure determined for KLK6 reveals a closed S1 pocket and a novel mechanism of zymogen activation. Overall these structures have proved highly informative in understanding the molecular mechanisms of the KKS and provide templates to design inhibitors for treatment of a variety of diseases.

Enhanced specificity of immunoblotting using radiolabeled antigen overlay: Studies of blood coagulation factor XII and prekallikrein in plasma

1986 ◽  
Vol 156 (1) ◽  
pp. 118-125 ◽  
Author(s):  
Bernhard Lämmle ◽  
Mauro Berrettini ◽  
John H. Griffin
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factor ◽  
Factor Xii

scholarly journals Cold-induced urticarial autoinflammatory syndrome related to factor XII activation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jörg Scheffel ◽  
Niklas A. Mahnke ◽  
Zonne L. M. Hofman ◽  
Steven de Maat ◽  
Jim Wu ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Gene Mutations ◽  
Coagulation Factor ◽  
Hek293 Cells ◽  
Receptor Protein ◽  
Local Source ◽  
Factor Xii ◽  
Mutant Proteins ◽  
Hereditary Autoinflammatory Diseases ◽  
Immune Pathway

AbstractHereditary autoinflammatory diseases are caused by gene mutations of the innate immune pathway, e.g. nucleotide receptor protein 3 (NLRP3). Here, we report a four-generation family with cold-induced urticarial rash, arthralgia, chills, headache and malaise associated with an autosomal-dominant inheritance. Genetic studies identify a substitution mutation in gene F12 (T859A, resulting in p.W268R) which encodes coagulation factor XII (FXII). Functional analysis reveals enhanced autocatalytic cleavage of the mutated protein and spontaneous FXII activation in patient plasma and in supernatant of transfected HEK293 cells expressing recombinant W268R-mutated proteins. Furthermore, we observe reduced plasma prekallikrein, cleaved high molecular weight kininogen and elevated plasma bradykinin. Neutrophils are identified as a local source of FXII. Interleukin-1β (IL-1β) is upregulated in lesional skin and mononuclear donor cells exposed to recombinant mutant proteins. Treatment with icatibant (bradykinin-B2-antagonist) or anakinra (interleukin-1-antagonist) reduces disease activity in patients. In conclusion, our findings provide a link between contact system activation and cytokine-mediated inflammation.

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