aminiacid selenocysteine and pyrrolysine
TRANSCRIPT
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Presentation onPresentation on::Expanding Genetic Code: Expanding Genetic Code:
Selenocysteine and PyrrolysineSelenocysteine and Pyrrolysine
Submitted to: Submitted by:
Dr. Jawaid Ahsan Shweta Kumari(Dept. Of Biological Science) M.Sc Bioinformatics
2nd semesterRoll no- 21Session: 2014-16
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Selenocystine:Selenocystine:The 21The 21stst amino acid amino acid
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IntroductionIntroduction
When the triplet nature of the genetic code was discovered, it was thought that there are only 20 amino acids determined by four nucleotides of the universal genetic code and that each of the 64 triplet codon has only one sense.
Selenium initialy believed to be toxic(more than sulfur).
1954: 1st report of Se requirement for function of bacterial formate dehydrogenase.
1959: 1st paper addressing Selenocystine.
1972: 1st biochemical studies on role of Se at enzyme level.
1986: key study implicating UGA as codon for Sec.
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IntroductionIntroduction. . .
21st proteogenic amino acid
Discoverd by biochemist THERESA STADTMANTHERESA STADTMAN at National Health of Institute.
Exist naturally in all kingdoms of life as a building block of selenoproteins
Present in several enzymes, egeg. Glutathione peroxidase, thioredoxine reductase, formate dehydrogenases, glycine reductase, selenophosphate synthase1 and some hydrogenases.
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StructureStructure
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PropertiesProperties
3 letter code Sec
1 letter code U
Codon UGAIUPAC Name 3-selanyl-2-aminopropanoic acid
Other name Selenium cystine, L-selenocystine
Molecular formula C3H7NO2Se
Molar mass 168.05 g/mol
Pka 5.47
pI 5.47
Melting point 143-146°C
polor acidic
Water Solubility 5 mg/L
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Unique feature of SecUnique feature of Sec
Other unique features of Sec, not shared by any of the other 20 common amino acids, derive from the Atomic weight and Chemical properties of selenium and the particular occurance and properties of its stable and radioactive isotopes.
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Cystine v/s SelenocystineCystine v/s Selenocystine
Sec contain seleniumselenium in the place of sulphur of Cys.
Sec has both lower pka (5.47) & lower reduction potential than Cys.
Sec is strong nucleophilic than Cys.
““These prorerties make it very These prorerties make it very suitable in protein, involved in suitable in protein, involved in antioxidant activity”.antioxidant activity”.
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BiosynthesisBiosynthesis The biosynthesis of this amino acid occurs on the tRNA which needs
to be first acylated with serine and then is subsequently transformed into selenocysteine by an enzyme synthase that further utilizes selenophosphate in the form of selenium donor and the cofactor pyridoxal phosphate.
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UGA codonUGA codon●UGA : termination codon and Sec codonSec codon.
●Discovered by BockBock in 1986 in bacterial formate dehydrogenase (FDH).
●In vivo studies confirmed that Sec tRNA [Ser] Sec recognize the UGA codon in both bacteria and eukaryotes.
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In ProkaryotesIn Prokaryotes● In prokayotes, an operon consisting of four genes known as the Sel operon is
also necessary for the incorporation of selenocysteine into proteins.
Genes of the sel operon
● sel A- converts serine to dehydroalanine
● sel B- codes for an EF-Tu like translation factor
● sel C- codes for the specific selenocysteine tRNA
● sel D- “activates” HSe-
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In EukaryotesIn Eukaryotes● Eukayotes do not contain Sel operon.
● Sec Insertion Sequence (SECIS) element play important role in translation.
● Other factors are:
● SBP2- SECIS binding protein.
● EEFsec- traslation factor,help in binding to ribosome.
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SourcesSources
Selenocysteine is found in proteins and in variety of foods of either animal origin or plant origin.
Animal originAnimal origin: Selenocysteine animal sources are meat, poultry, chicken, egg, cheese fish, seafood and turkey.
Plant origin: Selenocysteine of plant origin contains wheat, oats, corn, rice, nuts especially of Brazil nuts, soybeans.
Selenocysteine is available in the food in the form of selenomethionineselenomethionine.
In some foodstuff it occurs in the form of selenate.
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FunctionsFunctions
The important functions of selenocysteine in proteins are its antioxidantantioxidant activityactivity. This is due to its lower pKa and higher reduction potential.
It is also used in the preparation of variety of vitaminsvitamins and lots of other supplements.
It is also fortified with livestock feeds.
Our body utilizes selenocysteine to form selenium, which is believe to play important role in preventing mercury toxicitymercury toxicity as well as enhance liver functionsenhance liver functions.
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Importance of Sec for health:Importance of Sec for health: Biological role of seleniumBiological role of selenium
In 1930 selenium was found respontibal for sever human disease (US).
Cardiomiopathy was recorded in children and young woman (China,1930),called Keshan diseaseKeshan disease.
Deficient with selenium have lean body mass, prone to premature aging or to heart disease.
Selinium has cancer prevention effect (mediobiological and clinical report 1970-1990).
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Importance of Sec for health:Importance of Sec for health: Biological role of seleniumBiological role of selenium
Regulation of thyroyid hormone.
It has been discovered that HIV-1 encodes a functional selenoprotein. Patients with HIV have been shown to have a lower than average blood plasma selenium level.
Deficiancy of this element cause viral infection (transform avirulent strain into a virulent one).
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PyrrolysinePyrrolysineThe 22The 22ndnd amino acid amino acid
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IntroductionIntroduction
Recently discovered amino acid.
Considered as 22nd proteinogenic amino acid.
Discovered by mass spectrometric analysis and crystallographic approaches by scientist at Ohio State University in 2002.
Research is published in march 31st issue of the journal nature.
Indication of presence of this were given by structural analysis of monomethylamine Methanosarcina barkeriMethanosarcina barkeri.
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StructureStructure
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Properties
3- letter code Pyl
1 letter code O
Genetic codon UAG
Molecular formula C12H21N3O3
Molecular weight 255.313 g/mol
Boiling point 546.9 ± 50 °C at 760mmHg
Polar Weak basic
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Lysine V/s Pyrrolysine
●Pyl is similar to Lys, but with an added pyrroline ringpyrroline ring linked the end of Lys side chain (stretching from (stretching from NH2 toNH)NH2 toNH).
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BiosynthesisBiosynthesis
● Pyrrolysine is synthesized in vivo by joining two molecules of L-lysine.
● One molecule of lysine is first converted to (3R)-3-Methyl-D-ornithine, which is then ligated to a second lysine.
● An NH2 group is eliminated, followed by cyclization and dehydration step to yield L-pyrrolysineL-pyrrolysine
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Ambigous property of UAGAmbigous property of UAG● UAG: stop codon (amber) & code fo Pyl.
● Two genes are required in order to make out of UAG stop codon a “normal” amino acid encoding codon, which are PylTPylT and PylSPylS.
● Next to the 2 required genes PYLIS sequencePYLIS sequence (PyrroLysine Insertion Sequence) is also essential.
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FunctionsFunctions
Pyrrolysine reactivity with nucleophiles suggests the ability to participate in corrinoid dependent methylamine methyl-transferase reactions by interacting with either the methaloamine substrate or product.
Used by some methanogenic archaea and one known bacterium (Methanosarcina barkeri), in enzymes that are part of their methane-producing metabolism.
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ReferencesReferences
http://www.dailyhealthmagazine.com/selenocysteine/
● http://www.researchgate.net/topic/selenocysteine
● http://www.rcsb.org/pdb/101/motm.do?momID=104
● https://etd.ohiolink.edu/ap/10?0::NO:10:P10_ACCESSION_NUM:osu1318533705
● http://researchnews.osu.edu/archive/pyrrolysine.htm
● http://www.chemspider.com/Chemical-Structure.4574156.html
● http://www.jbc.org/content/280/21/20740.long
http://en.wikipedia.org/wiki/Pyrrolysine
http://www.dailyhealthmagazine.com/pyrrolysine/
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