4z50

Crystal Structure of Multidrug Resistant HIV-1 Protease Clinical Isolate PR20D25N with Tucked Flap

spinqualitylabelsall models 4z50, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4z50 is a 4 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.45Å Ligands: CL, GOL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q0PQ60_9HIV1 Publication Abstract from PubMed 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. Conformational variation of an extreme drug resistant mutant of HIV protease.,Shen CH, Chang YC, Agniswamy J, Harrison RW, Weber IT J Mol Graph Model. 2015 Sep 8;62:87-96. doi: 10.1016/j.jmgm.2015.09.006. PMID:26397743 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Immunodeficiency virus protease 3D structures

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