6ixd

X-ray crystal structure of bPI-11 hiv-1 protease complex

spinqualitylabelsall models 6ixd, resolution 1.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ixd is a 2 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 1Å Ligands: B0F, CL, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5RZ08_9HIV1 Publication Abstract from PubMed Protease inhibitors are used as both research tools and therapeutics. Many of these inhibitors consist of substrate amino acid sequence-derived structure with a transition state mimic to interact with the active site of the protease, suppressing enzymatic activity. However, once they bind, macrodilution or protein denaturation is required to remove them, limiting their usage. In this study, we describe a removable protease inhibitor, which is a directly biotinylated analogue to control the activities of HIV-1 protease and human cathepsin D. In the substrate cleavage assay, we observed that the nanomolar inhibitory activities were lost upon the addition of streptavidin, while the enzymatic activities sufficiently recovered. HIV-1 protease mixed with the removable inhibitor, avoiding autolysis, was still active to be detected by adding streptavidin after one year at room temperature. We also observed that the inhibitor was an effective eluent for the simple detection of the activity of proteases purified from human serum and cells. These results demonstrate that direct biotinylation of protease inhibitors could be a novel method for controlling the enzymatic activity from OFF to ON. We proposed the phenomenon that binding equilibrium of inhibitor was shifted from protease to streptavidin with higher affinity, named "inhibitor stripping action by affinity competition", or ISAAC. We anticipate that ISAAC could be applicable for preservatives of proteases and activity-based diagnosis of protease related diseases. Furthermore, removable inhibitor to be designed for targeted proteases changing the inhibitor structure may elucidate enzymatic activity in intrinsic form with natural modifications from various biological samples. Acquired Removability of Aspartic Protease Inhibitors by Direct Biotinylation.,Hidaka K, Adachi M, Tsuda Y Bioconjug Chem. 2019 Apr 22. doi: 10.1021/acs.bioconjchem.9b00195. PMID:30990716 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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