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

ChemMedChem
Supaporn SeetahaKoichi Kato

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.

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Citations

Jun 4, 2019·Biological & Pharmaceutical Bulletin·Maho Yagi-Utsumi
Aug 7, 2020·Chemical Biology & Drug Design·Supaphorn SeetahaKiattawee Choowongkomon
Nov 10, 2017·Essays in Biochemistry·Marta G CarneiroGregg Siegal
Oct 24, 2020·Chembiochem : a European Journal of Chemical Biology·Siriluk RatanabunyongSupa Hannongbua
Jan 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li Shi, Naixia Zhang
Dec 19, 2020·International Journal of Molecular Sciences·Tatiana V IlinaRieko Ishima

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