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Rapid identification of ligand-binding sites by using an assignment-free NMR approach.

Abstract：

:In this study, we developed an assignment-free approach for rapid identification of ligand-binding sites in target proteins by using NMR. With a sophisticated cell-free stable isotope-labeling procedure that introduces (15)N- or (13)C-labels to specific atoms of target proteins, this approach requires only a single series of ligand titrations with labeled targets. Using titration data, ligand-binding sites in the target protein can be identified without time-consuming assignment procedures. We demonstrated the feasibility of this approach by using structurally well-characterized interactions between mitogen-activated protein (MAP) kinase p38α and its inhibitor 2-amino-3-benzyloxypyridine. Furthermore, we confirmed the recently proposed fatty acid binding to p38α and confirmed the fatty acid-binding site in the MAP kinase insert region.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Kodama Y,Takeuchi K,Shimba N,Ishikawa K,Suzuki E,Shimada I,Takahashi H

doi

10.1021/jm4014357

subject

Has Abstract

pub_date

2013-11-27 00:00:00

pages

9342-50

issue

22

eissn

0022-2623

issn

1520-4804

journal_volume

56

pub_type

杂志文章

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