Acid incorporation mechanisms

B. Humans cannot synthesize folic acid (A) diet is their main source. Sulfonamides selectively inhibit microbially synthesized folic acid. Incorporation (B) of PABA into microbial folic acid is competitively inhibited by sulfonamides. The TMP-SMX combination is synergistic because it acts at different steps in microbial folic acid synthesis. All sulfonamides are bacteriostatic. Inhibition of the transpeptidation reaction (C) involved in the synthesis of the bacterial cell wall is the basic mechanism of action of (3-lac-tam antibiotics Changes in DNA gyrases (D) and active efflux transport system are mechanisms for resistance to quinolones. Structural changes (E) in dihydropteroate synthetase and overproduction of PABA are mechanisms of resistance to the sulfonamides. 

The molecular mechanism of local anesthesia, the location of the local anesthetic dibucaine in model membranes, and the interaction of dibucaine with a Na+-channel inactivation gate peptide have been studied in detail by 2H- and 1H-NMR spectroscopy [24]. Model membranes consisted of PC, PS, and PE. Dibucaine was deuterated at H9 and H3 of the butoxy group and at the 3-position of the quinoline ring. 2H-NMR spectra of the multilamellar dispersions of the lipid mixtures were obtained. In addition, spectra of deuterated palmitic acids incorporated into mixtures containing cholesterol were obtained and the order parameter, SCD, for each carbon... 

The recent studies of Hansen et al51 and Wittmann et al,109 revealed a new mechanism for lipidation of lipopeptide biosynthesis such as mycosubtilin or daptomycin biosynthesis by application of ESI-FTMS. Both papers describe that fatty acid incorporation is catalyzed by an A domain with fatty acid specificity in the loading module of the mycosubtilin NRPS (Figure 15) or by a preassembly line A and T domain in daptomycin biosynthesis (Figure 16). 

In addition, Tang et alw characterized a new mechanism for D-amino acid incorporation into NRP chains by NRPS, which was previously thought to happen only by epimerization of T domain-tethered L-amino acid... 

Complete elucidation of the mechanisms by which ricin kills target cells remains an area of active study, but it is clear that the A -glycosidase activity of RTA is the essential triggering event. Inhibition of protein synthesis precedes other detectable alterations in target cell biochemistry. Ricin blocks amino acid incorporation in cmde microsome preparations before changes occur in energy metabohsm or oxidative phosphorylation the toxin has essentially no effect on mitochondrial respiration in isolated mitochondria or tumor cells (Waller et al., 1966 Dirheimer et al., 1968 Lin et al., 1971). Likewise, the first observable cytotoxic effect of ricin in cell culture is typically the inhibition of protein synthesis, followed by a reduction in DNA synthesis (Lin et al., 1970 Lin et al., 1971 Onozaki et al., 1972 Refsnes et al., 1974 Nicolson et al., 1975 Olsnes et al., 1976 Refsnes et al., 1977). 

Although the accuracy of translation (approximately one error per 104 amino acids incorporated) is lower than those of DNA replication and transcription, it is remarkably higher than one would expect of such a complex process. The principal reasons for the accuracy with which amino acids are incorporated into polypeptides include codon-anticodon base pairing and the mechanism by which amino acids are attached to their cognate tRNAs. The attachment of amino acids to tRNAs, considered the first step in protein synthesis, is catalyzed by a group of enzymes called the aminoacyl-tRNA synthetases. The precision with which these enzymes esterify each specific amino acid to the correct tRNA is now believed to be so important for accurate translation that their functioning has been referred to collectively as the second genetic code. 

Thiostrepton family members are biosynthesized by extensive modification of simple peptides. Thus, from amino acid incorporation studies, the somewhat smaller (mol wt 1200) nosiheptide, which contains five thiazole rings, a trisubstituted indole, and a trisubstituted pyridine, is speculated to arise from a simple dodecapeptide. This work shows that the thiazole moieties arise from the condensation of serine with cysteine (159,160). Only a few reports on the biosynthesis of the thiostrepton family are available (159,160). Thiostrepton is presently used in the United States only as a polyantimicrobial veterinary ointment (Panalog, Squibb), but thiazole antibiotics have, in the past, been used as feed additives in various parts of the world. General (158) and mechanism of action (152) reviews on thiostrepton are available. 

Aso et al. [95] studied a model system in order to obtain basic information on the mechanism of amino acid incorporation during an enzymatic modification reaction in the presence of papain. They found that the amino acid ester reacted as a nucleophile in the aminolysis of the acyl-enzyme intermediate to result in the formation of new peptides. Several proteases used in enzymatic peptide bond synthesis are known to form transitory acyl-enzyme intermediates during the hydrolysis of proteins. However, the acyl groups can be transferred to other nucleophiles (amino terminals of peptides or amino acids), synthesizing new peptide bonds [71]. With full knowledge of the above-mentioned facts, covalent amino acid enrichment of proteins can result in... 

The research was focused on the acid leaching mechanism of goethite with nickel incorporated into goethite structure totally. Therefore, it was necessary to examine the synthesized nickeliferous goethite. 

IV. Mechanism of Amino Acid Incorporation into Proteins. 203... 

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