Protein synthesis inhibitor
Encyclopedia
While a broad interpretation of this definition could be used to describe nearly any antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
, in practice, it usually refers to substances that act at the ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
level (either the ribosome itself or the translation factor), taking advantages of the major differences between prokaryotic and eukaryotic ribosome structures.
Toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
s such as ricin
Ricin
Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally occurring protein. A dose as small as a few grains of salt can kill an adult. The LD50 of ricin is around 22 micrograms per kilogram Ricin , from the castor oil plant Ricinus communis, is a highly toxic, naturally...
also function via protein synthesis inhibition. Ricin acts at the eukaryotic 60S
60S
60S is the large ribosomal subunit in eukaryotes. It corresponds to 50S in prokaryotes.It consists of the following:* 5S* 28S* 5.8SThe following is a list of proteins contained within the 60S ribosome:...
.
Examples:
- NeomycinNeomycinNeomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951...
- Geneticin, also called G418
Mechanism
In general, protein synthesis inhibitors work at different stages of prokaryotic mRNA translationProkaryotic translation
Prokaryotic translation is the process by which messenger RNA is translated into proteins in prokaryotes.-Initiation:Initiation of translation in prokaryotes involves the assembly of the components of the translation system which are: the two ribosomal subunits , the mRNA to be translated, the...
into proteins, like initiation, elongation (including aminoacyl tRNA entry, proofreading
Proofreading (biology)
The term proofreading is used in genetics to refer to the error-correcting processes, first proposed by John Hopfield and Jacques Ninio, involved in DNA replication, immune system specificity, enzyme-substrate recognition among many other processes that require enhanced specificity...
, peptidyl transfer, and ribosomal translocation
Ribosomal translocation
Ribosomal translocation is a step in both:*Eukaryotic elongation and*Prokaryotic elongation, during translation of messenger RNA into proteins...
) and termination:
Earlier stages
- RifampicinRifampicinRifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
inhibits prokaryotic DNA transcriptionProkaryotic transcriptionProkaryotic transcription is the process in which messenger RNA transcripts of genetic material in prokaryotes are produced, to be translated for the production of proteins. Prokaryotic transcription occurs in the cytoplasm alongside translation. Unlike in eukaryotes, prokaryotic transcription and...
into mRNA by inhibiting DNA-dependent RNA polymeraseRNA polymeraseRNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
by binding its beta-subunit.
Initiation
- LinezolidLinezolidLinezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
acts at the initiation stage, probably by preventing the formation of the initiation complex, although the mechanism is not fully understood.
Aminoacyl tRNA entry
- Tetracyclines and TigecyclineTigecyclineTigecycline is a glycylcycline antibiotic developed by Francis Tally and marketed by Wyeth under the brand name Tygacil. It was given a U.S. Food and Drug Administration fast-track approval and was approved on June 17, 2005...
(a glycylcyclineGlycylcyclineGlycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection...
related to tetracyclines) block the A site on the ribosome, preventing the binding of aminoacyl tRNAs.
Proofreading
- Aminoglycosides, among other potential mechanisms of action, interfere with the proofreadingProofreading (biology)The term proofreading is used in genetics to refer to the error-correcting processes, first proposed by John Hopfield and Jacques Ninio, involved in DNA replication, immune system specificity, enzyme-substrate recognition among many other processes that require enhanced specificity...
process, causing increased rate of error in synthesis with premature termination.
Peptidyl transfer
- ChloramphenicolChloramphenicolChloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...
blocks the peptidyl transfer step of elongation on the 50S ribosomal subunit in both bacteria and mitochondria. - Macrolides (as well as inhibiting ribosomal translocation and other potential mechanisms) bind to the 50s ribosomal subunits, inhibiting peptidyl transfer.
- Quinupristin/dalfopristinQuinupristin/dalfopristinQuinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium....
act synergistically, with dalfopristin, enhancing the binding of quinupristin, as well as inhibiting peptidyl transfer. Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide, as well as causing incomplete chains to be released.
Ribosomal translocation
- MacrolideMacrolideThe macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered...
s, clindamycinClindamycinClindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
and aminoglycosides (with all these three having other potential mechanisms of action as well), have evidence of inhibition of ribosomal translocationRibosomal translocationRibosomal translocation is a step in both:*Eukaryotic elongation and*Prokaryotic elongation, during translation of messenger RNA into proteins...
. - Fusidic acidFusidic acidFusidic acid is a bacteriostatic antibiotic that is often used topically in creams and eyedrops, but may also be given systemically as tablets or injections...
prevents the turnover of elongation factorElongation factorElongation factors are a set of proteins that facilitate the events of translational elongation, the steps in protein synthesis from the formation of the first peptide bond to the formation of the last one.Elongation is the most rapid step in translation:...
G (EF-GEF-GEF-G or elongation factor G is one of the prokaryotic elongation factors.-Function:The factor EF-G catalyzes the translocation of the tRNA and mRNA down the ribosome at the end of each round of polypeptide elongation. Homologous to EF-Tu + tRNA, EF-G also binds to the ribosome in its GTP-bound...
) from the ribosomeRibosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
.
Termination
- Macrolides and clindamycinClindamycinClindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
(both also having other potential mechanisms) cause premature dissociation of the peptidyl-tRNA from the ribosome. - PuromycinPuromycinPuromycin is an antibiotic that is a protein synthesis inhibitor by inhibiting translation.-Inhibition of translation:Puromycin is an aminonucleoside antibiotic, derived from the Streptomyces alboniger bacterium, that causes premature chain termination during translation taking place in the...
has a structure similar to that of the tyrosinylTyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
aminoacyl-tRNA. Thus, it binds to the ribosomal A site and participates in peptide bond formation, producing peptidyl-puromycin. However, it does not engage in translocation and quickly dissociates from the ribosome, causing a premature termination of polypeptide synthesis. - StreptograminStreptograminStreptogramins are a class of antibiotics.Streptogramins are effective in the treatment of vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus , two of the most rapidly-growing strains of multidrug-resistant bacteria...
s also cause premature release of the peptide chain.
Binding site
The following antibiotics bind to the 30S subunit of the ribosomeRibosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
:
- AminoglycosideAminoglycosideAn aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...
s - Tetracyclines
The following antibiotics bind to the 50S ribosomal subunit:
- ChloramphenicolChloramphenicolChloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...
- ErythromycinErythromycinErythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
- ClindamycinClindamycinClindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
- LinezolidLinezolidLinezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
- TelithromycinTelithromycinTelithromycin is the first ketolide antibiotic to enter clinical use. It is used to treat mild to moderate respiratory infections. Telithromycin is sold under the brand name of Ketek....
- StreptograminStreptograminStreptogramins are a class of antibiotics.Streptogramins are effective in the treatment of vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus , two of the most rapidly-growing strains of multidrug-resistant bacteria...
s - RetapamulinRetapamulinRetapamulin is a topical antibiotic developed by GlaxoSmithKline. It is the first drug in the new class of pleuromutilin antibiotics to be approved for human use...