Misc. antibiotics and diseases
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- Polio virus
- Proteolysis of eIF4 - inhibits eukaryotic translation, allows its own mRNA to be translated
- Diphtheria toxin
- Inhibits the translocation step during eukaryotic translation elongation; Causes ADP ribosylation of EF2-translocase
- How much diphtheria toxin is needed to be effective?
- Only 1 molecule can modify all EF2 proteins, which are ATP dependent for translocation.
- EF2 is the eukaryotic analog of:
- Prokaryotic EF-G
- What modification does Diphtheria toxin cause in the EF-2 molecule?
- ADP-ribosylation of a His residue causes it to become a Diphthamide residue.
- Streptomycin is what type of antibiotic
- Aminoglycoside
- Action of aminoglycosides:
-
-inhibit translation initiation
-misreading of mRNA - Action of tetracycline:
- Binds 30S subunit; inhibits binding of aminoacyl-tRNAs.
- Chloramphenicol mechanism:
-
-50S ribosome subunit
-Inhibits peptidyl transferase - Action of Erythromycin:
-
-50S subunit
-Inhibits translocation - Puromicin
-
-Premature chain termination -Analog of aminoacyl-tRNA
-Inhibits both Prok+Euk - What organisms are affected by puromycin?
- Both euks and proks
- Action of Cyclohexamide:
-
-60S ribosome (euks)
-Inhibits peptidyl transferase activity - What causes erythromycin resistence in Staph?
- Plasmid born methylase causes mutation that blocks binding of the drug.
- Scurvy
- decrease in hydroxyproline synthesis; lack of enzyme activity necessary for collagen stability
- Type IV Ehlers Danlos
- lysyl hydroxylase deficiency
- anticancer drug that binds major groove - intercalates to inhibit transcription:
- Actinomycin D
- cisplatin
- introduces bent dna by inducing intrastrand cross bridges; inhibits cell growth.
- HDPF
- hered. persistence of fetal hb -> normally shut off by naturally occuring dna triple helix shuts off gene; mutation destabilizes triple helix and causes it to stay on; assoc. w/ Sickle cell disease
- novobiocin and ciprofloxacin
-
inhibit bacterial topoisomerase ii
cipro --> anthrax (b. anthracis) - doxorubicin and etoposide
- inhibit eukaryotic topo II - treat cancer
- a-amanitin
- mushroom toxin that inhibits RNAP in eukaryotes
- Which RNAP does a-amanitin inhibit most strongly?
- RNAP II
- What drugs inhibit transcription?
-
RADDC
rifampin
alpha amanitin
daunorubicin
dactinomycin
cordycepin - mechanism of rifampin:
- binds B subunit of bacterial RNAP; prevents transcription - used to treat Mycobact. TB
- mechanism of actinomycin D (dactinomycin)
- intercalates minor groove between two GC base pairs
- mechanism of daunorubicin
- intercalation
- mechanism of cordycepin
- lacks 3'OH; terminates elongation