Bihani SC, Das A, Prashar V, Ferrer JL, Hosur MV
Resistance Mechanism revealed by Crystal Structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S. [JOURNAL ARTICLE]
Biochem Biophys Res Commun 2009 Aug 28.
Nelfinavir is an inhibitor of HIV-1 protease, and is used for treatment of patients suffering from HIV/AIDS. However, treatment results in drug resistant mutations in HIV-1 protease. N88D and N88S are two such mutations which occur in the non-active site region of the enzyme. We have determined crystal structures of unliganded N88D and N88S mutants of HIV-1 protease to resolution of 1.65 A and 1.8 A respectively. These structures refined against synchrotron data lead to R-factors of 0.1859 and 0.1780 respectively. While structural effects of N88D are very subtle, the mutation N88S has caused a significant conformational change in D30, an active site residue crucial for substrate and inhibitor binding.
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