Question

The following drugs impair gene expression in cells. Outline the specific inhibitory mechanism for each.

Erythromycin

Alpha-amanitin

Tiamulin

Tavaborole

Flucytosine

Answer 1

Erythromycin :

It is an antibiotic which inhibits the growth of bacteria at higher concentrations. It binds to the 50S subunit of bacterial ribosomes and inhibits protein synthesis through structural modification of the ribosomes.

Alpha amanitin

Alpha amanitin inhibits bacterial growth by interfering with the bridge helix in RNA polymerase II. This interference hinds with the translocation of RNA polymerase over DNA which is needed to vacate the site for the next round of transcription. Alpha amanitin limits the RNA polymerase mobility and reduces its overall turnover rate.

Flucytosine:

Flucytosine, a pyrimadine analogue inside the fungus is converted into cytostatic fluorouracil which is subject to several steps of activation. Finally it is converted into 5- fluorouridinetriphosphate. This compound interferes with purine and pyrimidine uptake which hinders with transcription and inhibits protein synthesis.

Flucytosine also gets coverted into 5-fluorodeoxyuridinemonophosphate which is a non-competitive inhibitor of thymidylate synthetase thus inhibiting DNA synthesis in fungi.

Tavabarole :

Tavabarole acts by inhibiting Leucyl-tRNA synthetase , which is an essential fungal enzyme required for protein synthesis and catalysis of ATP- dependent transfer of L-Leucine onto tRNALeu .

Tiamulin :

Tiamulin is a semisynthetic diterpene antiobiotic which selectively inhibits Cyt P-450 intermediate complex which plays an important role in drug metabolism.

In addition, Tiamulin inhibits protein synthesis by binding to 50S subunit of ribosomes