Localization of ligands within human carbonic anhydrase II using ¹⁹F pseudocontact shift analysis.

ABSTRACT: Unraveling the native structure of protein-ligand complexes in solution enables rational drug design. We report here the use of ¹⁹F pseudocontact shift (PCS) NMR as a method to determine fluorine positions of high affinity ligands bound within the drug target human carbonic anhydrase II with high accuracy. Three different ligands were localized within the protein by analysis of the obtained PCS from simple one-dimensional ¹⁹F spectra with an accuracy of up to 0.8 Å. In order to validate the PCS, four to five independent magnetic susceptibility tensors induced by lanthanide chelating tags bound site-specifically to single cysteine mutants were refined. Least-squares minimization and a Monte-Carlo approach allowed the assessment of experimental errors on the intersectio

SUBMITTER: Zimmermann K 

PROVIDER: S-EPMC6530540 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature