Antibiotics and toxins that inhibit protein synthesis

antibiotics

evolved as natural weapons used by microorganisms (mainly bacteria and fungi) to kill or outcompete other microorganisms

humans use them as tools to combat pathogens or do research

no chemical or biochemical property that defines tham ll, only common feature is that they can impair some biochemical activity

a particular one usually has a very precise activity and some biological specificity

because of its critical function, the ribosome is a

frequent target for natural toxins that impair or suppress protein synthesis

edeine

affects initiation in both bacteria and euks

binds to E and P sites, prevents stabilization of initiator aminoacyl-tRNA

avilamycin

affects initiation in bacteria

binds to large subunit, prevents assembly with small subunit

aminoglycosides

affects elongation in bacteria and euks

binds to A site, includes incorrect codon-anticodon recognition

bind to 30S ribosomal subunit

impair proofreading, resulting in production of faulty proteins

streptomycin

affects elongation in bacteria

binds S12 protein, affects specificity when loading aa-tRNA into A site

chloramphenicol

affects elongation in bacteria

binds A site, inhibits peptidyl transferase reaction

bind to 50S ribosomal subunit, prevent peptide bond formation, stop protein synthesis

micrococcin

affects translocation in bacteria

binds A site, interferes with binding of initiation and elongation factors, affecting both initiation and translocation

fusidic acid

affects translocation in bacteria

prevents translocation by binding EF-G when complexed with ribosome

tetracyclines

one of the major classes of protein synthesis-inhibiting antibacterials

bind to the 30S ribosomal subunit

block binding of tRNAs, thereby inhibiting protein synthesis

puromycin

both this and aminoacyl-tRNA have a reactive NH2 group that acts as a nucleophile when appropriately positioned in the A site for attack on the ester linkage of peptidyl-tRNA in the P site

reaction is a dead-end reaction leading to chain termination

ricin (and shiga) toxin

glycosidase enzyme which specifically cleaves the purine from an A residue of the 28S rRNA

target occurs on a section of rRNA that is universally conserved among eukaryotes, therefore essential for function

interaction with eEF2 is abolished and translocation cannot occur

diphtheria toxin

exotoxin produced by pathogenic strains of C. diphtheriae bacteria, gene for it comes from a lysogenic prophage that integrates its gencome with C. diphtheriae plasmids

gene translated and secreted as a single, 535-residue polypeptide chain and consists of two major subunits, A and B

A subunit carries catalytic domain, B subunit comprises receptor binding and transmembrane domains

selectively ADP-ribosylating EF-2, attenuating protein synthesis and leading to cell death within a matter of hours, highly toxic

antimicrobial peptides (AMPs)

small peptides of 15-70 aa residues generated from post-translational processing of large precursors

found in bacteria, archaea, euks—many produced by insects, amphibians, mammals, and plants

part of the innate immunity and evolved to target pathogens commonly found by the host in their habitats

most work by disrupting membranes and membrane proteins

proline-rich AMPs

specific class of AMP, can enter cell and inhibit protein synthesis

apidaecin

AMP produced by honeybees and wasps that inhibits translation in bacteria by trapping release factors on ribosome

Api137

binds to ribosome after RF1 and RF2 catalyzes release of complete protein and traps RF1 and RF2, thereby preventing their turnover

trapping them depletes their available pool, causing stalling of most ribosomes at the stop codons, unable to release nascent proteins