3KT5

Crystal Structure of N88S mutant HIV-1 Protease

Summary for 3KT5

• Entry DOI: 10.2210/pdb3kt5/pdb
• Related: 3KT2
• Descriptor: Protease (2 entities in total)
• Functional Keywords: drug resistant, mutation, hiv-1 protease, n88s, nelfinavir, hydrolase, protease
• Biological source: Human immunodeficiency virus type 1 (HIV-1); More
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585
• Total number of polymer chains: 1
• Total formula weight: 21788.59

Authors

Bihani, S.C.,Das, A.,Prashar, V.,Ferrer, J.L.,Hosur, M.V. (deposition date: 2009-11-24, release date: 2010-02-16, Last modification date: 2024-05-29)

Primary citation

Bihani, S.C.,Das, A.,Prashar, V.,Ferrer, J.L.,Hosur, M.V.
Resistance mechanism revealed by crystal structures of unliganded nelfinavir-resistant HIV-1 protease non-active site mutants N88D and N88S.
Biochem.Biophys.Res.Commun., 389:295-300, 2009

PubMed 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 1.65A and 1.8A, 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.

PubMed: 19720046
DOI: 10.1016/j.bbrc.2009.08.138

Experimental method

X-RAY DIFFRACTION (1.801 Å)