Application of Site-Specific Spin Labeling for NMR Detecting Inhibitor-Induced Conformational Change of HIV-1 Reverse Transcriptase.
 

Application of Site-Specific Spin Labeling for NMR Detecting Inhibitor-Induced Conformational Change of HIV-1 Reverse Transcriptase.

Related Articles Application of Site-Specific Spin Labeling for NMR Detecting Inhibitor-Induced Conformational Change of HIV-1 Reverse Transcriptase.

ChemMedChem. 2016 Jan 25;

Authors: Seetaha S, Yagi-Utsumi M, Yamaguchi T, Ishii K, Hannongbua S, Choowongkomon K, Kato K

Abstract
Paramagnetism-assisted nuclear magnetic resonance (NMR) techniques can provide long-range structural information complemented with local information derived from chemical-shift perturbation and nuclear Overhauser effect data. Here, we address the application of paramagnetic relaxation enhancement (PRE) to detect inhibitor-induced conformational change of a drug target protein using human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) as a model protein. Using a site-specific spin-labeled HIV-1 RT mutant with selective (13) C labeling, conformation-dependent PREs were successfully observed reflecting the stabilization of an open conformation of this enzyme caused by inhibitor binding. This study demonstrates that the paramagnetism-assisted NMR approach offers an alternative strategy in protein-based drug screening to identify allosteric inhibitors of a target protein.


PMID: 26804978 [PubMed - as supplied by publisher]



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