Ovotransferrin

Last updated
Ovotransferrin
PDB 1gvc EBI.jpg
PDB 1gvc EBI
Identifiers
Organism Gallus gallus
Symbol?
UniProt P02789
Search for
Structures Swiss-model
Domains InterPro
Asparagine L-Asparagin - L-Asparagine.svg
Asparagine
Basic N-glycan Basic N-glycan.svg
Basic N-glycan

Ovotransferrin (conalbumin) is a glycoprotein of egg white albumen. [1] Egg white albumen is composed of multiple proteins, of which ovotransferrin is the most heat reliable. It has a molecular weight of 76,000 daltons and contains about 700 amino acids. Ovotransferrin makes up approximately 13% of egg albumen (in contrast to ovalbumin, which comprises 54%). [2] As a member of the transferrin and metalloproteinase family, ovotransferrin has been found to possess antibacterial and antioxydant and immunomodulatory properties, arising primarily through its iron (Fe3+) binding capacity by locking away a key biochemical component necessary for micro-organismal survival. Bacteria starved of iron are rendered incapable of moving, making ovotransferrin a potent bacteriostatic.

Contents

Structure

Ovotransferrin is folded in a way that forms two lobes (N- and C- terminals) and each lobe consists of a binding site. Each lobe is then divided into two domains of 160 amino acid residues. Its structure also consists of fifteen disulfide crosslinks and no free sulfhydryl groups. Disulfide groups stabilize the tertiary structures of proteins. Transferrins are iron binding proteins and acute phase reactants of animal serum. It has a binding log of 15 at a pH of 7 or above, meaning that the iron binding capacity of ovotransferrin rapidly decreased at a pH that is less than 6. This family is also known for their role in cell maturation by transporting essential nutrients to developing embryos. Ovotransferrin functions as an antimicrobial agent and transports iron to the developing embryo. Because they bind to iron, this makes it difficult for harmful bacteria to be nutritionally satisfied with them so it acts as an antimicrobial.

The primary sequence of ovotransferrin is similar to that of many serum transferrins found in other species. Recently, scientists have discovered a blood serum transferrin in humans, that binds iron like ovotransferrin and which shows 50% homology to ovotransferrin, i.e., they have similar amino acid composition and carbohydrate content. At the C- lobe, human serum has two N-glycans while the hen ovotransferrin has a single N-glycan. Consequently, structurally this protein differs from its serum counterpart because of its glycosylation pattern. These proteins are said to be glycosylated because they have carbohydrates attached to them. Glycosylation is the most common covalent modification (formation of chemical bonds) that occurs in living organisms. This process is determined by the structure of the protein backbone and the carbohydrate attachment site.

In addition, ovotransferrin is glycosylated by the N-linkage to the amino acid known as asparagine, meaning that the glycan, the carbohydrate chain, is attached to the nitrogen on the amino acid. Asparagine, found abundantly in asparagus (hence, its name), is one of twenty of the most common amino acids and was the first amino acid to be isolated. While ovotransferrin identifies with its family, there are two types of ovotransferrin proteins: apo and holo. Apo-Ovotransferrin is deprived of iron and holo-Ovotransferrin is saturated with iron. Because the apo-ovotransferrin is iron-deprived, it is easily destroyed by physical and chemical treatments.

Function and mechanism

Biologically, conalbumin isolates and sequesters metallic contaminants in the egg white. [3] Ovotransferrin is functionally and structurally analogous to mammalian lactoferrin [4] A recent study has shown superior performance of ovotransferrin when compared to lactoferrin in its capability to deliver iron without accumulation or inducing gastric irritability, rendering ovotransferrin as an excellent potential iron carrier for the treatment of Iron-deficiency anemia (IDA). Ovotransferrin showed superior physiological iron delivery over lactoferrin in a gastric barrier model. This data holds much promise for ovotransferrin's use in food supplements, with dual functionality as both antimicrobial and iron delivery mechanism. [5]

Role in disease and therapy

Numerous studies have identified dual anti-osteoporotic properties of ovotransferrin, both reducing bone resorption and promoting bone formation. [6] Beyond this, ovotransferrin shows promise as a drug carrier with potential applications in cancer treatment. [7] Indeed, ovotransferrin alone is toxic to cancer cells in-vitro. Its antioxidant and anti-inflammatory properties may also make ovotransferrin a viable treatment for cardiovascular disease. [8] [9]

See also

Related Research Articles

An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life forms, the nine amino acids humans cannot synthesize are valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, threonine, histidine, and lysine.

<span class="mw-page-title-main">Iron deficiency</span> State in which a body lacks enough iron to supply its needs

Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key component of the hemoglobin protein, acting as a transport medium for electrons within the cells in the form of cytochromes, and facilitating oxygen enzyme reactions in various tissues. Too little iron can interfere with these vital functions and lead to morbidity and death.

<span class="mw-page-title-main">Glycoprotein</span> Protein with oligosaccharide modifications

Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.

<span class="mw-page-title-main">Transferrin</span> Mammalian protein found in Homo sapiens

Transferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.

Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule in order to form a glycoconjugate. In biology, glycosylation usually refers to an enzyme-catalysed reaction, whereas glycation may refer to a non-enzymatic reaction.

<span class="mw-page-title-main">Acute-phase protein</span> Class of proteins involved in inflammation

Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase or decrease in response to inflammation. This response is called the acute-phase reaction. The acute-phase reaction characteristically involves fever, acceleration of peripheral leukocytes, circulating neutrophils and their precursors. The terms acute-phase protein and acute-phase reactant (APR) are often used synonymously, although some APRs are polypeptides rather than proteins.

<span class="mw-page-title-main">Lactoferrin</span> Mammalian protein found in Homo sapiens

Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions. Lactoferrin is also present in secondary granules of PMNs and is secreted by some acinar cells. Lactoferrin can be purified from milk or produced recombinantly. Human colostrum has the highest concentration, followed by human milk, then cow milk (150 mg/L).

<span class="mw-page-title-main">Siderophore</span> Iron compounds secreted by microorganisms

Siderophores (Greek: "iron carrier") are small, high-affinity iron-chelating compounds that are secreted by microorganisms such as bacteria and fungi. They help the organism accumulate iron. Although a widening range of siderophore functions is now being appreciated, siderophores are among the strongest (highest affinity) Fe3+ binding agents known. Phytosiderophores are siderophores produced by plants.

<span class="mw-page-title-main">Human serum albumin</span> Albumin found in human blood

Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric.

<span class="mw-page-title-main">Albumin</span> Family of globular proteins

Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins are commonly found in blood plasma and differ from other blood proteins in that they are not glycosylated. Substances containing albumins are called albuminoids.

Iron-binding proteins are carrier proteins and metalloproteins that are important in iron metabolism and the immune response. Iron is required for life.

<span class="mw-page-title-main">Tej P. Singh</span> Indian biophysicist (born 1944)

Tej Pal Singh is an Indian biophysicist known for his work in the fields of rational structure-based drug design, structural biology of proteins and X-ray crystallography. He has played an active role in the development of drug design in the fields of antibacterial therapeutics, tuberculosis, inflammation, cancer and gastropathy.

Polysialic acid is an unusual posttranslational modification that occurs on neural cell adhesion molecules (NCAM). Polysialic acid is considerably anionic. This strong negative charge gives this modification the ability to change the protein's surface charge and binding ability. In the synapse, polysialation of NCAM prevents its ability to bind to NCAMs on the adjacent membrane.

Prevotella is a genus of Gram-negative bacteria.

Feline coronavirus (FCoV) is a positive-stranded RNA virus that infects cats worldwide. It is a coronavirus of the species Alphacoronavirus 1, which includes canine coronavirus (CCoV) and porcine transmissible gastroenteritis coronavirus (TGEV). FCoV has two different forms: feline enteric coronavirus (FECV), which infects the intestines, and feline infectious peritonitis virus (FIPV), which causes the disease feline infectious peritonitis (FIP).

Cross-reactive carbohydrate determinants (CCDs) play a role in the context of allergy diagnosis. The terms CCD or CCDs describe protein-linked carbohydrate structures responsible for the phenomenon of cross-reactivity of sera from allergic patients towards a wide range of allergens from plants and insects. In serum-based allergy diagnosis, antibodies of the IgE class directed against CCDs therefore give the impression of polysensitization. Anti-CCD IgE, however, does not seem to elicit clinical symptoms. Diagnostic results caused by CCDs are therefore regarded as false positives.

<span class="mw-page-title-main">Intelectin</span>

Intelectins are lectins expressed in humans and other chordates. Humans express two types of intelectins encoded by ITLN1 and ITLN2 genes respectively. Several intelectins bind microbe-specific carbohydrate residues. Therefore, intelectins have been proposed to function as immune lectins. Even though intelectins contain fibrinogen-like domain found in the ficolins family of immune lectins, there is significant structural divergence. Thus, intelectins may not function through the same lectin-complement pathway. Most intelectins are still poorly characterized and they may have diverse biological roles. Human intelectin-1 (hIntL-1) has also been shown to bind lactoferrin, but the functional consequence has yet to be elucidated. Additionally, hIntL-1 is a major component of asthmatic mucus and may be involved in insulin physiology as well.

N-glycosyltransferase is an enzyme in prokaryotes which transfers individual hexoses onto asparagine sidechains in substrate proteins, using a nucleotide-bound intermediary, within the cytoplasm. They are distinct from regular N-glycosylating enzymes, which are oligosaccharyltransferases that transfer pre-assembled oligosaccharides. Both enzyme families however target a shared amino acid sequence asparagine—-any amino acid except proline—serine or threonine (N–x–S/T), with some variations.

<span class="mw-page-title-main">Glycan-protein interactions</span> Class of biological intermolecular interactions

Glycan-Protein interactions represent a class of biomolecular interactions that occur between free or protein-bound glycans and their cognate binding partners. Intramolecular glycan-protein (protein-glycan) interactions occur between glycans and proteins that they are covalently attached to. Together with protein-protein interactions, they form a mechanistic basis for many essential cell processes, especially for cell-cell interactions and host-cell interactions. For instance, SARS-CoV-2, the causative agent of COVID-19, employs its extensively glycosylated spike (S) protein to bind to the ACE2 receptor, allowing it to enter host cells. The spike protein is a trimeric structure, with each subunit containing 22 N-glycosylation sites, making it an attractive target for vaccine search.

GlycoRNAs are small non-coding RNAs with sialylated glycans.

References

  1. "OVOTRANSFERRIN: The nutraceutical protein with antimicrobial, antioxidant and immunomodulatory properties". Bioseutica B.V.
  2. Wu J, Acero-Lopez A (2012). "Ovotransferrin: Structure, bioactivities, and preparation". Food Research International. 46 (2): 480–487. doi:10.1016/j.foodres.2011.07.012.
  3. "Conalbumin". steadyhealth. Archived from the original on 2011-07-16.
  4. Giansanti F, Leboffe L, Angelucci F, Antonini G (November 2015). "The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food". Nutrients. 7 (11): 9105–9115. doi: 10.3390/nu7115453 . PMC   4663581 . PMID   26556366.
  5. Galla R, Grisenti P, Farghali M, Saccuman L, Ferraboschi P, Uberti F (October 2021). "Ovotransferrin Supplementation Improves the Iron Absorption: An In Vitro Gastro-Intestinal Model". Biomedicines. 9 (11): 1543. doi: 10.3390/biomedicines9111543 . PMC   8615417 . PMID   34829772.
  6. Shang N, Wu J (March 2018). "Egg White Ovotransferrin Shows Osteogenic Activity in Osteoblast Cells". Journal of Agricultural and Food Chemistry. 66 (11): 2775–2782. doi:10.1021/acs.jafc.8b00069. PMID   29502401.
  7. Ibrahim HR, Kiyono T (December 2009). "Novel anticancer activity of the autocleaved ovotransferrin against human colon and breast cancer cells". Journal of Agricultural and Food Chemistry. 57 (23): 11383–11390. doi:10.1021/jf902638e. PMID   19886663.
  8. Lee N, Cheng J, Enomoto T, Nakano YO (December 2009). "One peptide derived from hen ovotransferrin as pro-drug to inhibit angiotensin converting enzyme". Journal of Food and Drug Analysis. 57 (23): 11383–11390. doi:10.38212/2224-6614.2505.
  9. Chen S, Jiang H, Peng H, Wu X, Fang J (2018). "The Utility of Ovotransferrin and Ovotransferrin-Derived Peptides as Possible Candidates in the Clinical Treatment of Cardiovascular Diseases". Oxidative Medicine and Cellular Longevity. 2017: 6504518. doi: 10.1155/2017/6504518 . PMC   5366766 . PMID   28386310.