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Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses
by
Francischetti, Ivo M. B.
, Eum, Jai Hoon
, Kotsyfakis, Michail
, Champagne, Donald E.
, Tsujimoto, Hitoshi
, Strand, Michael R.
in
Amino Acid Sequence
/ Amino acids
/ Analysis
/ Animals
/ Anticoagulants
/ Aquatic insects
/ Arthropoda
/ Arthropods
/ Base Sequence
/ Biology
/ Biosensors
/ Black flies
/ Blindness
/ Blood
/ Blood Coagulation - drug effects
/ Catalytic Domain
/ Cathepsin G
/ Cathepsin G - antagonists & inhibitors
/ Chemical bonds
/ Clotting
/ Coagulation
/ Diptera
/ Disease
/ Disease transmission
/ DNA Mutational Analysis
/ Elastase
/ Enzyme Inhibitors - pharmacology
/ Enzymes
/ Factor Xa Inhibitors
/ Female
/ Gene Expression Regulation, Enzymologic
/ Glands
/ Inflammation
/ Inhibitory Concentration 50
/ Insect Proteins - chemistry
/ Insect Proteins - metabolism
/ Kinetics
/ Male
/ Mammals
/ Medicine
/ Molecular Sequence Data
/ Onchocerca volvulus
/ Onchocerciasis
/ Pancreatic Elastase - antagonists & inhibitors
/ Pathogens
/ Pharmacology
/ Plasmin
/ Polypeptides
/ Protease inhibitors
/ Proteins
/ Recombinant Proteins - chemistry
/ River blindness
/ Saliva
/ Salivary glands
/ Salivary Glands - metabolism
/ Salivary Proteins and Peptides - chemistry
/ Salivary Proteins and Peptides - metabolism
/ Serine
/ Simuliidae
/ Simuliidae - metabolism
/ Simulium vittatum
/ Surface Plasmon Resonance
/ Thrombin
/ Vectors
2012
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Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses
by
Francischetti, Ivo M. B.
, Eum, Jai Hoon
, Kotsyfakis, Michail
, Champagne, Donald E.
, Tsujimoto, Hitoshi
, Strand, Michael R.
in
Amino Acid Sequence
/ Amino acids
/ Analysis
/ Animals
/ Anticoagulants
/ Aquatic insects
/ Arthropoda
/ Arthropods
/ Base Sequence
/ Biology
/ Biosensors
/ Black flies
/ Blindness
/ Blood
/ Blood Coagulation - drug effects
/ Catalytic Domain
/ Cathepsin G
/ Cathepsin G - antagonists & inhibitors
/ Chemical bonds
/ Clotting
/ Coagulation
/ Diptera
/ Disease
/ Disease transmission
/ DNA Mutational Analysis
/ Elastase
/ Enzyme Inhibitors - pharmacology
/ Enzymes
/ Factor Xa Inhibitors
/ Female
/ Gene Expression Regulation, Enzymologic
/ Glands
/ Inflammation
/ Inhibitory Concentration 50
/ Insect Proteins - chemistry
/ Insect Proteins - metabolism
/ Kinetics
/ Male
/ Mammals
/ Medicine
/ Molecular Sequence Data
/ Onchocerca volvulus
/ Onchocerciasis
/ Pancreatic Elastase - antagonists & inhibitors
/ Pathogens
/ Pharmacology
/ Plasmin
/ Polypeptides
/ Protease inhibitors
/ Proteins
/ Recombinant Proteins - chemistry
/ River blindness
/ Saliva
/ Salivary glands
/ Salivary Glands - metabolism
/ Salivary Proteins and Peptides - chemistry
/ Salivary Proteins and Peptides - metabolism
/ Serine
/ Simuliidae
/ Simuliidae - metabolism
/ Simulium vittatum
/ Surface Plasmon Resonance
/ Thrombin
/ Vectors
2012
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Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses
by
Francischetti, Ivo M. B.
, Eum, Jai Hoon
, Kotsyfakis, Michail
, Champagne, Donald E.
, Tsujimoto, Hitoshi
, Strand, Michael R.
in
Amino Acid Sequence
/ Amino acids
/ Analysis
/ Animals
/ Anticoagulants
/ Aquatic insects
/ Arthropoda
/ Arthropods
/ Base Sequence
/ Biology
/ Biosensors
/ Black flies
/ Blindness
/ Blood
/ Blood Coagulation - drug effects
/ Catalytic Domain
/ Cathepsin G
/ Cathepsin G - antagonists & inhibitors
/ Chemical bonds
/ Clotting
/ Coagulation
/ Diptera
/ Disease
/ Disease transmission
/ DNA Mutational Analysis
/ Elastase
/ Enzyme Inhibitors - pharmacology
/ Enzymes
/ Factor Xa Inhibitors
/ Female
/ Gene Expression Regulation, Enzymologic
/ Glands
/ Inflammation
/ Inhibitory Concentration 50
/ Insect Proteins - chemistry
/ Insect Proteins - metabolism
/ Kinetics
/ Male
/ Mammals
/ Medicine
/ Molecular Sequence Data
/ Onchocerca volvulus
/ Onchocerciasis
/ Pancreatic Elastase - antagonists & inhibitors
/ Pathogens
/ Pharmacology
/ Plasmin
/ Polypeptides
/ Protease inhibitors
/ Proteins
/ Recombinant Proteins - chemistry
/ River blindness
/ Saliva
/ Salivary glands
/ Salivary Glands - metabolism
/ Salivary Proteins and Peptides - chemistry
/ Salivary Proteins and Peptides - metabolism
/ Serine
/ Simuliidae
/ Simuliidae - metabolism
/ Simulium vittatum
/ Surface Plasmon Resonance
/ Thrombin
/ Vectors
2012
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Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses
Journal Article
Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses
2012
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Overview
Black flies (Diptera: Simuliidae) feed on blood, and are important vectors of Onchocerca volvulus, the etiolytic agent of River Blindness. Blood feeding depends on pharmacological properties of saliva, including anticoagulation, but the molecules responsible for this activity have not been well characterized.
Two Kunitz family proteins, SV-66 and SV-170, were identified in the sialome of the black fly Simulium vittatum. As Kunitz proteins are inhibitors of serine proteases, we hypothesized that SV-66 and/or -170 were involved in the anticoagulant activity of black fly saliva. Our results indicated that recombinant (r) SV-66 but not rSV-170 inhibited plasma coagulation. Mutational analysis suggested that SV-66 is a canonical BPTI-like inhibitor. Functional assays indicated that rSV66 reduced the activity of ten serine proteases, including several involved in mammalian coagulation. rSV-66 most strongly inhibited the activity of Factor Xa, elastase, and cathepsin G, exhibited lesser inhibitory activity against Factor IXa, Factor XIa, and plasmin, and exhibited no activity against Factor XIIa and thrombin. Surface plasmon resonance studies indicated that rSV-66 bound with highest affinity to elastase (K(D) = 0.4 nM) and to the active site of FXa (K(D) = 3.07 nM). We propose the name \"Simukunin\" for this novel protein.
We conclude that Simukunin preferentially inhibits Factor Xa. The inhibition of elastase and cathepsin G further suggests this protein may modulate inflammation, which could potentially affect pathogen transmission.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Analysis
/ Animals
/ Biology
/ Blood
/ Blood Coagulation - drug effects
/ Cathepsin G - antagonists & inhibitors
/ Clotting
/ Diptera
/ Disease
/ Elastase
/ Enzyme Inhibitors - pharmacology
/ Enzymes
/ Female
/ Gene Expression Regulation, Enzymologic
/ Glands
/ Insect Proteins - metabolism
/ Kinetics
/ Male
/ Mammals
/ Medicine
/ Pancreatic Elastase - antagonists & inhibitors
/ Plasmin
/ Proteins
/ Recombinant Proteins - chemistry
/ Saliva
/ Salivary Glands - metabolism
/ Salivary Proteins and Peptides - chemistry
/ Salivary Proteins and Peptides - metabolism
/ Serine
/ Thrombin
/ Vectors
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