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Nitrophorins are
hemoprotein A hemeprotein (or haemprotein; also hemoprotein or haemoprotein), or heme protein, is a protein that contains a heme prosthetic group. They are a very large class of metalloproteins. The heme group confers functionality, which can include oxygen ...
s found in the
saliva Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...
of blood-feeding insects.


Purpose and description

Saliva of the blood-sucking bug ''
Rhodnius prolixus ''Rhodnius prolixus'' is the principal triatomine vector of the Chagas parasite due to both its sylvatic and domestic populations in northern South America as well as to its exclusively domestic populations in Central America. It has a wide ran ...
'' 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 (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
(NO) ligated to the ferric heme
iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...
(Fe3+).
Histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
, which is released by the
host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County * Host Island, in the Wilhelm Archipelago, Antarctica People * ...
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 Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel ...
. The salivary nitrophorin from the
hemiptera Hemiptera (; ) is an order of insects, commonly called true bugs, comprising more than 80,000 species within groups such as the cicadas, aphids, planthoppers, leafhoppers, assassin bugs, bed bugs, and shield bugs. They range in size from ...
n ''Cimex lectularius'' (
bedbug Bed bugs are parasitic insects from the genus ''Cimex'', which are micropredators that feed on blood, usually at night. Their bites can result in a number of health impacts, including skin rashes, psychological effects, and allergic symptom ...
) 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 Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last comm ...
.


Structures

The crystal structures of several nitrophorin complexes are known. The ''Rhodnius prolixus'' nitrophorin structures reveal
lipocalin The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids, and most lipocalins are also able to bind to complexed iron (via siderophores or flavonoids) as well as heme. Th ...
-like eight-stranded β-barrel, three α-helices and two disulfide bonds, with heme inserted into one end of the barrel. Members of th
lipocalin family
are known to bind a variety of small hydrophobic ligands, including
biliverdin Biliverdin (from the Latin for green bile) is a green tetrapyrrolic bile pigment, and is a product of heme catabolism.Boron W, Boulpaep E. Medical Physiology: a cellular and molecular approach, 2005. 984–986. Elsevier Saunders, United States. ...
, in a similar fashion. The heme iron is ligated to
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...
residue (His-59). The position of His-59 is restrained through water-mediated
hydrogen bond In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...
to the carboxylate of
aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protei ...
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 p''K''a. 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 ''b''5. 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. NO can bind both to heme Fe3+ and to proximal Cys-60 ligand causing reversible ''S''-nitrosylation.


References


External links and further reading

* * * * - X-ray structure of ''Rhodnius prolixus'' nitrophorin 1 complexed with histamine and PO43− * - X-ray structure of ''
Cimex lectularius ''Cimex lectularius'', or the common bed bug, is a species of Cimicidae. Its primary hosts are humans, and it is one of the world's major "nuisance pests." Although bed bugs can be infected with at least 28 human pathogens, no studies have fou ...
'' nitrophorin in complex with NO
Montfort Lab
- Nitrophorin research @
University of Arizona The University of Arizona (Arizona, U of A, UArizona, or UA) is a Public university, public Land-grant university, land-grant research university in Tucson, Arizona, United States. Founded in 1885 by the 13th Arizona Territorial Legislature, it ...
, Tucson, USA {{Authority control Hemoproteins