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1 .Protein forming amino acids - 20 amino acids Posttranscriptional modification 2. Non-standard Amino acids
The phosphoproteins are usually classified into two families, phosphotyrosine (pTyr)-containing and phosphoserine (pSer)/phosphothreonine (pThr)-containing sequences .
They are phosphorylated and dephosphorylated by different categories of kinases (e.g., pThr/pSer kinase and pThr kinase) and phosphatases . Recent studies discovered a few modular domains that particularly recognize pThr/pSer- or pThr-containing sequences, such as the breast-cancer-associated protein BRCA1 C-terminal (BRCT) repeats, WW domain and forkhead-associated (FHA) domain .
Phosphorylation and sulfation Some of the tyrosine residues can be tagged with a phosphate group by protein kinases. It is referred to as phosphotyrosine. Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST).
Phosphoserine
Modifications, like phosphorylation: A common mechanism for controlling the behavior of a protein,; For eg. activating or inactivating an enzyme.
Phosphoserine is an ester of serine and phosphoric acid catalyzed by various types of kinases. Phosphoserine is a component of many proteins as the result of posttranslational modificaations. Phosphorylation of proteins on serine and threonine residues has traditionally been viewed as a means to allosterically regulate catalytic activity.
Phosphothreonine The threonine residue is susceptible to numerous post-traslational modifications. The hydroxy side-chain can undergo Olinked glycosilation.
In addition, threonine residues undergo phosphorylation through the action of a threonine kinase. In its phosphorylated form, it can be referred to as phosphothreonine.
Among these uncommon amino acids are 4-hydroxyproline, a derivative of proline, and 5-hydroxylysine, derived from lysine.
4-hydroxyproline: Found in plant cell wall proteins; Synthesized in plant cells in response to stress. Hydroxyproline and Hydroxylysine are found in collagen, a fibrous protein of connective tissues. Found in capillaries, bone and cartilage. Proline and lysine are formed in the procollagen and It is hydroxylated in the presence of ascorbic acid. These hydroxylation help in the cross linking of the collagen molecules and thereby stabilizing structure of collagen.
Another important uncommon amino acid is -carboxyglutamate, found in (1) bloodclotting protein prothrombin and in (2) certain proteins that bind Ca2 as part of their biological function.
Desmosine is a complex molecule; It is a derivative of four Lys residues, and is found in the fibrous protein elastin.
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of vertebrates. In humans, elastin is encoded by the ELN gene. This desmosine is responsible for the rubber like properties of elastin.
Selenocysteine is a special case. This rare amino acid residue is introduced during protein synthesis .
Actually derived from serine, selenocysteine is a constituent of just a few known proteins. Selenocysteine has a structure similar to that of cysteine, but with an atom of selenium taking the place of the usual sulfur, forming a selenol group which is deprotonated at physiological pH. Present in several Enzymes (for example glutathione peroxidases, tetraiodothyronine 5' deiodinases, thioredoxin reductases, formate dehydrogenases, glycine reductases, selenophosphate synthetase 1, methionine-Rsulfoxide reductase B1 (SEPX1), and some hydrogenases)
Proteins that contain one or more selenocysteine residues are called selenoproteins. Solenocysteine (21-Sec -U) Pyrrolysine (22 Pyl -O)
N-Methylarginine is an inhibitor of nitric oxide synthase. Chemically, it is a methyl derivative of the amino acid arginine. It is used as a biochemical tool in the study of physiological role of nitric oxide. Nitric oxide transient in its function.
Nitric oxide, also known as nitrogen monoxide, is a molecule with chemical formula NO. It is a free radical. In mammals including humans, NO is an important cellular signaling molecule involved in many physiological and pathological processes. It is a powerful vasodilator with a short half-life of a few seconds in the blood. (Dissection) Long-known pharmaceuticals like nitroglycerine and amyl nitrite were discovered, more than a century after their first use in medicine, to be active through the mechanism of being precursors to nitric oxide. Low levels of nitric oxide production are important in protecting organs such as the liver from ischemic damage.
Acetyllysine (or acetylated lysine) is an acetyl-derivative of the amino acid lysine. There are multiple forms of acetyllysine .
Non-protein aminoacids: Some 300 additional amino acids have been found in cells. They have a variety of functions but are not constituents of proteins. Ornithine and citrulline deserve special note because they are key intermediates (metabolites) in the biosynthesis of arginine and in the urea cycle .
whereas other proteins, such as fibrin and vimentin are susceptible to citrullination during cell death and tissue inflammation.
Patients with rheumatoid arthritis often have detectable antibodies against proteins containing citrulline.
Although the origin of this immune response is not known, detection of antibodies reactive with citrulline (anticitrullinated protein antibodies) containing proteins or peptides is now becoming an important help in the diagnosis of rheumatoid arthritis. In recent studies, citrulline has been found to relax blood vessels.
In bacteria, such as E. coli, ornithine can be synthesized from Lglutamate. Ornithine is also the starting point for cocaine biosynthesis, when decarboxylased, then modified greatly by Cytochrome P450.
Potential medical uses Exercise fatigue L-Ornithine supplementation attenuated fatigue in subjects in a placebo controlled study using a cycle ergometer. The results suggested that L-ornithine has an antifatigue effect in increasing the efficiency of energy consumption and promoting the excretion of ammonia. Stress L-Ornithine reduced stress in mice and made them more sociable toward other mice as well as the scientists conducting the experiment. Cirrhosis L-ornithine-L-aspartate (LOLA), a stable salt of ornithine and aspartic acid, has been used in the treatment of cirrhosis. Weightlifting supplement Amino acid supplements, including L-ornithine, are frequently used by body-builders and weightlifters to increase levels of HGH. In a Finnish study, these supplements, in low doses, were not found to increase levels of growth hormone. However, the study did not administer the amino-acids while the subjects were fasting, an important requirement in testing for the effect of amino acids on HGH stimulation.
D-Aminoacids:
Post-translational modifications: Modification involves conversion of amino acids in peptide linkage the L- fprm to D-configurations.
D-amino acid containing peptides from Frog: Dermorphin: Heptapeptide: Tyr-D-Ala- Phe-Gly-Tyr-Pro-Ser amide
Deltrophin:
-Lys -Asn-
D-Alanine in Dermorphin was discovered when it was found that the synthetic peptide with the same sequence of L-amino acid was biologically inactive.
Non-standard amino acids that are found in proteins are formed by post-translational modification, which is modification after translation during protein synthesis. These modifications are often essential for the function or regulation of a protein; for example, the carboxylation of glutamate allows for better binding of calcium cations,[38] and the hydroxylation of proline is critical for maintaining connective tissues.[39] Another example is the formation of hypusine in the translation initiation factor EIF5A, through modification of a lysine residue.[40] Such modifications can also determine the localization of the protein, e.g., the addition of long hydrophobic groups can cause a protein to bind to a phospholipid membrane.[41]
Some nonstandard amino acids are not found in proteins. Examples include lanthionine, 2-aminoisobutyric acid, dehydroalanine, and the neurotransmitter gamma-aminobutyric acid. Nonstandard amino acids often occur as intermediates in the metabolic pathways for standard amino acids for example, ornithine and citrulline occur in the urea cycle, part of amino acid catabolism (see below).[42] A rare exception to the dominance of -amino acids in biology is the -amino acid beta alanine (3-aminopropanoic acid), which is used in plants and microorganisms in the synthesis of pantothenic acid (vitamin B5), a component of coenzyme A