BCH Exm 3, 4 - Crick's Central Dogma Part III Translation...

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Fig. 10-1, p.241 Crick’s Central Dogma, Part III: Translation Translation is the synthesis of proteins from mRNA ( Protein Biosynthesis ) The mature mRNA ( or transcript ) encodes for an ordered series of amino acids, or polypeptide chain The mRNA code is read by tRNAs at the ribosome, leading to the synthesis of a polypeptide chain
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Amino Acid Activation The activation of the amino acid and the formation of the aminoacyl-tRNA take place in two steps, both of which are catalyzed by the enzyme aminoacyl tRNA synthetase 1. The amino acid forms a covalent bond with an adenine nucleotide producing an aminoacyl-AMP 2. The aminoacyl is then transferred to the tRNA forming an aminoacyl- tRNA Amino acid + ATP aminoacyl-AMP + PPi Aminoacyl-AMP + tRNA aminoacyl-tRNA + AMP
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Amino Acid Activation: Step 1 Covalent attachment of the amino acid to ATP catalyzed by aminoacyl tRNA synthetase Aminoacyl-AMP is a mixed anhydride of a carboxylic acid and a phosphoric acid As anhydrides are reactive compounds, the free energy change for the hydrolysis of aminoacyl-AMP favors the second step of the reaction Another point that favors this process is the energy released when pyrophosphate (PP i ) is hydrolyzed to orthophosphate (P i )
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Amino Acid Activation: Step 2 Transfer of the aminoacyl to the tRNA catalyzed by aminoacyl tRNA synthetase An ester linkage is formed between the aminoacyl and either the 3’-hydroxyl or the 2’-hydroxyl of the ribose at the 3’ end of the tRNA There are two classes of aminoacyl tRNA synthetases; Class I loads the amino acid onto the 2’-hydroxyl and Class II loads the amino acid onto the 3’-hydroxyl
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Fig. 12-6, p.308
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Amino Acid Activation - Selectivity & Proofreading 1. A given tRNA will only bond to one amino acid 2. A unique aminoacyl-tRNA synthetase exists for each amino acid ( the aminoacyl- tRNA synthetase can function for all the different tRNA molecules for that amino acid ) 3. Specificity is aided by the fact that, during step one of amino acid activation, the aminoacyl-tRNA synthetase remains bound to the aminoacyl-AMP 4. If, for example, the isoleucine-tRNA synthetase forms a valine-AMP (instead of an isoleucine-AMP), an editing site in the isoleucine-tRNA synthetase can hydrolyze the incorrectly acylated valine-tRNA 5. The aminoacyl-tRNA synthetases specifically recognize binding sites on the tRNA, typically sites other than the acceptor stem or anti-codon
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Fig. 12-7, p.309 tRNA Tertiary Structure Numbers represent the consensus nucleotide sequence The locations of nucleotides recognized by the various aminoacyl-tRNA synthetases are indicated; shown within the boxes are the one-letter designations of the amino acids
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Fig. 12-1, p.302 Translation Chain Initiation
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Fig. 9-25, p.235
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