Nitrophorin
Encyclopedia
Nitrophorins are hemoprotein
s found in saliva
of blood-feeding
insects. Saliva of the blood-sucking bug Rhodnius prolixus
contains at least seven homologous nitrophorins, designated NP1 to NP7 in order of their relative abundance in the glands. As isolated, nitrophorins contain nitric oxide
(NO) ligated to the ferric heme iron
(Fe3+). Histamine
, which is released by the host
in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport NO to the feeding site. Dilution, binding of histamine and increase in pH
(from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of NO into the tissue where it induces vasodilatation.
The salivary nitrophorin from the hemiptera
n Cimex lectularius (bedbug
) has no sequence similarity to Rhodnius prolixus
nitrophorins but is homologous to the inositol-polyphosphate 5-phosphatase . It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent evolution
.
The crystal structures of several nitrophorin complexes are known. The Rhodnius prolixus
nitrophorin structures reveal lipocalin
-like eight-stranded β-barrel, three α-helices and two disulfide bonds, with heme inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin
, in a similar fashion. The heme iron is ligated to histidine
residue (His-59). The position of His-59 is restrained through water-mediated hydrogen bond
to the carboxylate of aspartic acid
residue (Asp-70). The His-59–Fe bond is bent ~15° out of the imidazole plane. Asp-70 forms an unusual hydrogen bond with one of the heme propionates, suggesting the residue
has an altered pKa
. In NP1-histamine structure, the planes of His-59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidized cytochrome b5.
The fold of nitrophorin from Cimex lectularius consists of central 11-stranded β-sandwich and seven peripheral α-helices. The heme is positioned between β-sheet and an α-helix, with heme iron ligated to cysteinate residue. Interestingly, NO can bind both to heme Fe3+ and to proximal Cys-60 ligand causing reversible S-nitrosylation.
nitrophorin 1 complexed with histamine and PO43- - X-ray structure of Cimex lectularius nitrophorin in complex with NO
Hemoprotein
A hemeprotein , or heme protein, is a metalloprotein containing a heme prosthetic group- an organic compound that allows a protein to carry out a function that it cannot do alone....
s found in saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
of blood-feeding
Hematophagy
Hematophagy is the practice of certain animals of feeding on blood...
insects. Saliva of the blood-sucking bug Rhodnius prolixus
Rhodnius prolixus
Rhodnius prolixus is the second most important triatomine vector of the Chagas parasite due to its efficient adaptation to the human domicile in northern South America, where sylvatic populations also exist, and in Central America where it is exclusively domestic...
contains at least seven homologous nitrophorins, designated NP1 to NP7 in order of their relative abundance in the glands. As isolated, nitrophorins contain nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
(NO) ligated to the ferric heme iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
(Fe3+). Histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, which is released by the host
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport NO to the feeding site. Dilution, binding of histamine and increase in pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
(from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of NO into the tissue where it induces vasodilatation.
The salivary nitrophorin from the hemiptera
Hemiptera
Hemiptera is an order of insects most often known as the true bugs , comprising around 50,000–80,000 species of cicadas, aphids, planthoppers, leafhoppers, shield bugs, and others...
n Cimex lectularius (bedbug
Bedbug
Cimicidae are small parasitic insects. The most common type is Cimex lectularius. The term usually refers to species that prefer to feed on human blood...
) has no sequence similarity to Rhodnius prolixus
Rhodnius prolixus
Rhodnius prolixus is the second most important triatomine vector of the Chagas parasite due to its efficient adaptation to the human domicile in northern South America, where sylvatic populations also exist, and in Central America where it is exclusively domestic...
nitrophorins but is homologous to the inositol-polyphosphate 5-phosphatase . It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent evolution
Convergent evolution
Convergent evolution describes the acquisition of the same biological trait in unrelated lineages.The wing is a classic example of convergent evolution in action. Although their last common ancestor did not have wings, both birds and bats do, and are capable of powered flight. The wings are...
.
The crystal structures of several nitrophorin complexes are known. The Rhodnius prolixus
Rhodnius prolixus
Rhodnius prolixus is the second most important triatomine vector of the Chagas parasite due to its efficient adaptation to the human domicile in northern South America, where sylvatic populations also exist, and in Central America where it is exclusively domestic...
nitrophorin structures reveal lipocalin
Lipocalin
The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture...
-like eight-stranded β-barrel, three α-helices and two disulfide bonds, with heme inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin
Biliverdin
Biliverdin is a green tetrapyrrolic bile pigment, and is a product of heme catabolism. It is the pigment responsible for a greenish color sometimes seen in bruises.- Metabolism :...
, in a similar fashion. The heme iron is ligated to histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
residue (His-59). The position of His-59 is restrained through water-mediated hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
to the carboxylate of aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
residue (Asp-70). The His-59–Fe bond is bent ~15° out of the imidazole plane. Asp-70 forms an unusual hydrogen bond with one of the heme propionates, suggesting the residue
has an altered pKa
Acid dissociation constant
An acid dissociation constant, Ka, is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid-base reactions...
. In NP1-histamine structure, the planes of His-59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidized cytochrome b5.
The fold of nitrophorin from Cimex lectularius consists of central 11-stranded β-sandwich and seven peripheral α-helices. The heme is positioned between β-sheet and an α-helix, with heme iron ligated to cysteinate residue. Interestingly, NO can bind both to heme Fe3+ and to proximal Cys-60 ligand causing reversible S-nitrosylation.
External links
- X-ray structure of Rhodnius prolixusRhodnius prolixus
Rhodnius prolixus is the second most important triatomine vector of the Chagas parasite due to its efficient adaptation to the human domicile in northern South America, where sylvatic populations also exist, and in Central America where it is exclusively domestic...
nitrophorin 1 complexed with histamine and PO43- - X-ray structure of Cimex lectularius nitrophorin in complex with NO
- Montfort Lab - Nitrophorin research @ University of Arizona, Tucson, USA