4Z4X
Crystal Structure of Multidrug Resistant HIV-1 Protease Clinical Isolate PR20D25N with Open Flap
Summary for 4Z4X
| Entry DOI | 10.2210/pdb4z4x/pdb |
| Related | 4Z50 |
| Descriptor | Protease (2 entities in total) |
| Functional Keywords | hiv-1 protease, hydrolase |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 21531.12 |
| Authors | Chang, Y.C.,Shen, C.-H.,Weber, I.T. (deposition date: 2015-04-02, release date: 2015-10-14, Last modification date: 2023-09-27) |
| Primary citation | Shen, C.H.,Chang, Y.C.,Agniswamy, J.,Harrison, R.W.,Weber, I.T. Conformational variation of an extreme drug resistant mutant of HIV protease. J.Mol.Graph.Model., 62:87-96, 2015 Cited by PubMed Abstract: Molecular mechanisms leading to high level drug resistance have been analyzed for the clinical variant of HIV-1 protease bearing 20 mutations (PR20); which has several orders of magnitude worse affinity for tested drugs. Two crystal structures of ligand-free PR20 with the D25N mutation of the catalytic aspartate (PR20D25N) revealed three dimers with different flap conformations. The diverse conformations of PR20D25N included a dimer with one flap in a unique "tucked" conformation; directed into the active site. Analysis of molecular dynamics (MD) simulations of the ligand-free PR20 and wild-type enzymes showed that the mutations in PR20 alter the correlated interactions between two monomers in the dimer. The two flaps tend to fluctuate more independently in PR20 than in the wild type enzyme. Combining the results of structural analysis by X-ray crystallography and MD simulations; unusual flap conformations and weakly correlated inter-subunit motions may contribute to the high level resistance of PR20. PubMed: 26397743DOI: 10.1016/j.jmgm.2015.09.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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