PHARMACOLOGY Study Guide - Topoisomerase Iv, Dna Gyrase, Quinolone

Prokaryotic topoisomerase II, also called DNA gyrase, is specifically inhibited by an antibiotic called novobiocin, which binds to the β subunit of the enzyme. This antibiotic inhibits bacterial DNA replication. What does DNA gyrase do and suggest why a compound that inhibits this enzyme would be an effective antibiotic.

1. DNA unwinding and topology

a. What is required for DNA unwinding at the replication fork?

b. What are DNA topoisomers? How is DNA topology related to the linking number, writhing and twist?

c. Why must the topology be changed during DNA unwinding?

d. What is required to change DNA topology?

e. What are the mechanistic differences between Type I and II topoisomerases? Similarities?

f. What are the consequences of topoisomerase II inhibition at different stages in the catalytic mechanism?