| Title | Resistance Mechanism revealed by Crystal Structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S. | | Author(s) | Bihani SC, Das A, Prashar V, Ferrer JL, Hosur MV | | Institution | Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai - 400085, India. | | Source | Biochem Biophys Res Commun 2009 Aug 28. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19720046 |
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