Sandbox Reserved 712: Difference between revisions
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The relative vitality values are defined as v = (K<sub>i</sub>k<sub>cat</sub>/K<sub>m</sub>)<sub>MUT</sub>/(K<sub>i</sub>k<sub>cat</sub>/K<sub>m</sub>)<sub>WT</sub>. It describes the relative ability of a PR species to hydrolyze its substrate when the inhibitor is present. This means the higher the vitality the more supports the mutated PR the viral replication. <ref name="Kinetic"> PMID:7626598 </ref> | The relative vitality values are defined as v = (K<sub>i</sub>k<sub>cat</sub>/K<sub>m</sub>)<sub>MUT</sub>/(K<sub>i</sub>k<sub>cat</sub>/K<sub>m</sub>)<sub>WT</sub>. It describes the relative ability of a PR species to hydrolyze its substrate when the inhibitor is present. This means the higher the vitality the more supports the mutated PR the viral replication. <ref name="Kinetic"> PMID:7626598 </ref> | ||
The relative vitality is related to the phenotypic changes in the susceptibility to [[darunavir]]. As one can see in the diagram, the more darunavir-associated mutations there are, the higher is the relative vitality (PR<sub>DRV4</sub> > PR<sub>DRV1</sub> > PR<sub>DRV2</sub> > PR<sub>DRV6</sub>). Due to the fact that PR<sub>DRV5</sub> does not have the key mutations, it has a low vitality value for [[darunavir]] and the structural related [[amprenavir]] in comparison to the other samples. The [[lopinavir]] pattern looks different than the overall pattern of darunavir and amprenavir, because it has a different structure and resistance profile than the others.(Fig1) <ref name="Molecular"> PMID:19535439 </ref> | The relative vitality is related to the phenotypic changes in the susceptibility to [[darunavir]]. As one can see in the diagram, the more darunavir-associated mutations there are, the higher is the relative vitality (PR<sub>DRV4</sub> > PR<sub>DRV1</sub> > PR<sub>DRV2</sub> > PR<sub>DRV6</sub>). Due to the fact that PR<sub>DRV5</sub> does not have the key mutations, it has a low vitality value for [[darunavir]] and the structural related [[amprenavir]] in comparison to the other samples. The [[lopinavir]] pattern looks different than the overall pattern of [[darunavir]] and [[amprenavir]], because it has a different structure and resistance profile than the others.(Fig1) <ref name="Molecular"> PMID:19535439 </ref> | ||
Despite the many mutations the k<sub>cat</sub> values were still between 30% and 50% of the wild-type value. In contrast the K<sub>m</sub> values of the mutants were (mostly) four- to eightfold higher than the wild-type PR. | Despite the many mutations the k<sub>cat</sub> values were still between 30% and 50% of the wild-type value. In contrast the K<sub>m</sub> values of the mutants were (mostly) four- to eightfold higher than the wild-type PR. | ||