1rev

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spinqualitylabelsall models 1rev, resolution 2.6Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HIV-1 REVERSE TRANSCRIPTASE

Overview

BACKGROUND: HIV reverse transcriptase (RT) is a key target of anti-AIDS, therapies. Structural studies of HIV-1 RT, unliganded and complexed with, different non-nucleoside inhibitors (NNIs), have pointed to a common mode, of binding and inactivation through distortion of the polymerase catalytic, site by NNIs containing two hinged rings. The mode of binding of the TIBO, family of inhibitors is of interest because these compounds do not fit the, two-hinged-ring model. RESULTS: The structure of HIV-1 RT complexed with, 9-chloro-TIBO (R82913) has been determined at 2.6 A resolution. As, reported for the lower resolution analysis of another TIBO compound, this, inhibitor binds at the same site as other NNIs, but our higher resolution, study reveals the Cl-TIBO is distorted from the conformation seen in, crystals of the inhibitor alone. This allows Cl-TIBO to mimic the binding, of NNIs containing two hinged rings. Inhibitor-protein interactions are, again predominantly hydrophobic and the protein conformation corresponds, to that seen in complexes with other tight-binding NNIs. CONCLUSIONS:, Although Cl-TIBO is chemically very different from other NNIs, it achieves, remarkable spatial equivalence and shape complementarity with other NNIs, on binding to RT. Comparison of the different RT-NNI complexes suggests, modifications to the TIBO group of inhibitors which might enhance their, binding and hence, potentially, their therapeutic efficacy.

About this Structure

1REV is a Protein complex structure of sequences from Human immunodeficiency virus 1 with MG and TB9 as ligands. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.

Reference

The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO: lessons for inhibitor design., Ren J, Esnouf R, Hopkins A, Ross C, Jones Y, Stammers D, Stuart D, Structure. 1995 Sep 15;3(9):915-26. PMID:8535785

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