Adenosine triphosphate synthetase mechanisms

For most amino acids, the ester linkage between the ct-COOH group of the amino acid and the 3 -terminal adenosine of a cognate tRNA is formed in a two-step mechanism catalyzed by an aminoacyl-tRNA synthetase (aaRS). ° In this so-called direct pathway, the aaRS first catalyzes the reaction of the amino acid with adenosine triphosphate (ATP), yielding the enzyme-bound high-energy intermediate aa AMP and PPi in the second step, this aaRS-bound intermediate reacts with tRNA to yield aa-tRNA and AMP (Figure 1). 

Animal and bacterial enzymes that utilize or synthesize carbamyl phosphate have activity with acetyl phosphate. Acyl phosphatase hydrolyzes both substrates, and maybe involved in the specific dynamic action of proteins. Ornithine and aspartic transcarbamylases also synthesize acetylornithine and acetyl aspartate. Finally, bacterial carbamate kinase and animal carbamyl phosphate synthetase utilize acetyl phosphate as well as carbamyl phosphate in the synthesis of adenosine triphosphate. The synthesis of acetyl phosphate and of formyl phosphate by carbamyl phosphate synthetases is described. The mechanism of carbon dioxide activation by animal carbamyl phosphate synthetase is reviewed on the basis of the findings concerning acetate and formate activation. 

In 1990, La wen and Zocher (49) described the purification and characterization of the enzyme cyclosporin synthetase, isolated from the mycelium of the strain T. inflatum NRRL 8044 (S 7939/45). This enzyme synthesizes cyclosporin A by a thiotemplate mechanism starting from the precursor amino acids in their unmethylated form, utilizing adenosine triphosphate ATP)/Mg, and with S-adenosyl-L-methionine as methyl donor. The first attempts (50) to establish the cell-firee synthesis of cyclosporin A were not successful, but they led to a partially enriched enzyme that could synthesize the diketopipcr-... 

Nonribosomal peptide synthesis means that the peptide is not produced by the tRNA-mRNA mechanism described in Chapter 28, Section 28.6. Each amino acid found in 224 is directly selected for incorporation into the growing peptide chain by one of the domains of surfactin synthetase, shown with the pendant SH groups. Substrate activation occurs after binding the amino acid, and the enzyme catalyzes the formation of an aminoacyl adenylate intermediate using Mg2+-ATP and release of a cofactor. Subsequently, the amino acid-O-AMP oxoester is converted into a thioester by a nucleophilic attack of the free thiol-bound cofactor of an adjacent PCP domain. (Note that ATP is adenosine triphosphate and AMP is adenosine monophosphate see Chapter 28, Section 28.5.)... 

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