Pactamycin

The universal antibiotic pactamycin targets a highly conserved region of 16S rRNA, contacting the tips of helices 23b and 24a in the central domain. Pactamycin folds up to mimic a RNA dinucleotide in that its... 

Ribosomal Protein Synthesis Inhibitors. Figure 4 The binding site of pactamycin on the 30S subunit. The positions of mRNA, the RNA elements H28, H23b, H24a, and the C-terminus of protein S7 are depicted in the E-site of the native 30S structure (left) and in the 30S-pactamycin complex (right). In the complex with pactamycin, the position of mRNA is altered (from Brodersen etal. [4] with copyright permission). 

Brodersen DE, Clemons WM, Carter AP et al (2000) The structural basis for the action of the antibiotics tetracycline, pactamycin and hygromycin B on the 30S ribosomal subunit. Cell 103 1143-1154... 

Dinos, G., Wilson, D. N., Teraoka, Y., Szaflarski, W., Fucini, P., Kalpaxis, D., and Nierhaus, K. H. (2004). Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin The universally conserved residues G693 and C795 regulate P-site RNA binding. Mol. Cell 13, 113-124. 

Geldanomycin, Rif.amycin, and Antibiotic A23187. — It is now clear that 3-amino-5-hydroxybenzoic acid (103) is the long-sought, key CyN intermediate involved in the biosynthesis of rifamycins and mitomycins. On the other hand, the C N intermediate involved in the biosynthesis of the 3-aminoacetophenone residue in pactamycin (101) is 3-aminobenzoic acid (100) (cf. Vol. 12, p.21). 

Inhibitors of translation - A number of the common inhibitors of prokaryotic translation are also effective in eukaryotic cells. They include pactamycin, tetracycline, and puromycin. Inhibitors that are effective only in eukaryotes include cycloheximide and diphtheria toxin. Cycloheximide inhibits the peptidyltransferase activity of the eukaryotic ribosome. Diphtheria toxin is an enzyme, coded for by a bacteriophage that is lysogenic in the bacterium Corynebacterium diphtheriae. It catalyzes a reaction in which NAD+ adds an ADP ribose group to a specially modified histidine in the translocation factor eEF2, the eukaryotic equivalent of EF-G (Figure 28.36). Because the toxin is a catalyst, minute amounts can irreversibly block a cell s protein synthetic machinery. As a result, pure diphtheria toxin is one of the most deadly substances known. 

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