protein drugs

Question 1

examples of targets for 30S ribosome

Answer 1

tetracyclins, streptomycin

Question 2

example of targets for the 50S ribosome

Answer 2

chloramphenicol, erythromycin

Question 3

action of spectinomycin

Answer 3

interferes with elongation factor G during translocation

Question 4

action of paramomycin and streptomycin

Answer 4

bind to 30S subunit near the A site for tRNA binding

Question 5

initiation of protein synthesis in bacteria

Answer 5

• first N-terminal AA = formylmethionine
• mRNA becomes attached to 30S which requires participation of a soluble protein, initiation factor 3
• formylmethionine-charged tRNA combines with mRNA-30S ribosomal complex, which requires initiation factors 1 and 2 and GTP
• 50S ribosomal unit becomes bound > GTP hydrolysed > initiation factors released

Question 6

elongation phase of protein synthesis in bacteria

Answer 6

2 of these require elongation factors & GTP:
- first 2 tRNAs orient appropriately, with attached AAs adjacent on the surface of the 50S portion of the ribosomes
- they become linked by a peptide bond by the peptidyltransferase activity associated with the 50S subunit
- carboxyl group of formylmethionine is linked to the amino group of the 2nd AA, and the dipeptide is attached to the 2nd tRNA, occupying the A site
- tRNA for formylmethionine moves from P to E site and is released. tRNA with dipeptide moves from A to P site and the 30S subunit moves one codon along the mRNA
- continues until a termination sequence signals that protein is complete

Question 7

tetracycline action

Answer 7

• oxygens of internucleotide phosphodiester links in 16S rRNA form electrostatic interactions directed through a Mg2+ ion to the bottom edge of tetracycline
• it blocks rotation of aminoacyl-tRNA into the A site
• so the aminoacyl-tRNA is prematurely released and the cycle is terminated without peptide bond formation

Question 8

aminoglycoside action

Answer 8

• bind to 30S ribosomal subunit and freeze the pre-initiation complex (subunit, mRNA and fmet-tRNA) so no further initiation can occur
• also slow protein synthesis that’s already been initiated and induce misreading of mRNA (so bactericidal)

Question 9

example of expanded spectrum macrolide

Answer 9

clarithromycin

Question 10

action of erythromycin & clarithromycin

Answer 10

• bind at entrance to export tunnel of 50S subunit and interact with 23S rRNA
• so there’s a 6-8 oligopeptidyl-tRNA buildup before elongation is blocked and prematurely terminated

Question 11

lincomycin action

Answer 11

direct peptidyltransferase inhibitor (so competitive with macrolides)

Question 12

which antibiotics bind to 23S rRNA in overlapping binding sites

Answer 12

• macrolides
• lincosamides (e.g. lincomycin)
• streptogramin B

Question 13

clindamycin action

Answer 13

• direct peptidyltransferase inhibitor
• interacts with A and P sites of peptidyltransferase centre, competing w the binding of loaded tRNA molecules

Question 14

chloramphenicol action

Answer 14

binds to 50S ribosomal subunit near the A site, preventing peptidyltransferase activity

Question 15

fusidic action

Answer 15

also binds to and inhibits elongation factor G, blocking translocation - but better because less side effects

Question 16

synercid action

Answer 16

• binds to 23S rRNA sites partially overlapping with those targeted by macrolides
• synergistic nonribosomal peptide combination (quinupristin + dalfopristin) which blocks polypeptide translocation @ 50S