AZT-resistant HIV-1 reverse transcriptase: Difference between revisions
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The excision mechanism has been shown to result from a set of mutations. [[Reverse transcriptase]] isolated from patients with AZT-resistant viruses do not typically have all of these mutations, however, combinations of the mutations give rise to high levels of resistance to AZT. AZT-resistant [[reverse transcriptase]] incorporates AZTTP just as efficiently as the wild-type, yet it has an improved ability to removed incorporated AZT from the 5' end of the template strand. A model that explains this process implies that because the addition of AZT to DNA destabilizes the closed complex, an AZT terminated primer has increased access to the active site so it can be excised. There are many complexities involved in this mechanism that are not currently understood. | The excision mechanism has been shown to result from a set of mutations. [[Reverse transcriptase]] isolated from patients with AZT-resistant viruses do not typically have all of these mutations, however, combinations of the mutations give rise to high levels of resistance to AZT. AZT-resistant [[reverse transcriptase]] incorporates AZTTP just as efficiently as the wild-type, yet it has an improved ability to removed incorporated AZT from the 5' end of the template strand. A model that explains this process implies that because the addition of AZT to DNA destabilizes the closed complex, an AZT terminated primer has increased access to the active site so it can be excised. There are many complexities involved in this mechanism that are not currently understood. | ||
The exclusion mechanism also results from a set of mutations. All amino acids involved in this mechanism exist in the finger or palm of [[reverse transcriptase]] in positions capable of affecting the binding of an incoming dNTP. There is little known about this mechanism, however, evidence suggests that some mutations cause changes in the hydrogen bonding network between the deoxyribose of an incoming dNTP and the enzyme. These changes increase the importance of the interactions of the enzyme with the 3'-OH. | The exclusion mechanism also results from a set of mutations. All amino acids involved in this mechanism exist in the finger or palm of [[reverse transcriptase]] in positions capable of affecting the binding of an incoming dNTP. There is little known about this mechanism, however, evidence suggests that some mutations cause changes in the hydrogen bonding network between the deoxyribose of an incoming dNTP and the enzyme. These changes increase the importance of the interactions of the enzyme with the 3'-OH and thus allow the mutant [[reverse transcriptase]] to better discriminate between normal dNTP which have 3'-OH and AZT which does not have a 3'-OH. | ||
==References== | ==References== | ||
