Structure Report for: 4C4X

Pilger, J., Mazur, A., Monecke, P., Schreuder, H., Elshorst, B., Langer, T., Schiffer, A., Krimm, I., Wegstroth, M., Lee, D., Hessler, G., Wendt, K.-U., Becker, S., Griesinger, C.

Title: A combination of spin diffusion methods for the determination of protein-ligand complex structural ensembles
Pilger J, Mazur A, Monecke P, Schreuder H, Elshorst B, Bartoschek S, Langer T, Schiffer A, Krimm I and Griesinger C <5 more author(s)> Pilger J, Mazur A, Monecke P, Schreuder H, Elshorst B, Bartoschek S, Langer T, Schiffer A, Krimm I, Wegstroth M, Lee D, Hessler G, Wendt KU, Becker S, Griesinger C (- 5)
Ref: Angew Chem Int Ed Engl, 54:6511, 2015 : PubMed
Abstract


ESTHER: Pilger_2015_Angew.Chem.Int.Ed.Engl_54_6511
PubMedSearch: Pilger 2015 Angew.Chem.Int.Ed.Engl 54 6511
PubMedID: 25877959
Gene_locus related to this paper: human-EPHX2
Inhibitor(s) related to this paper: ZINC395065-W9L-4C4Z, ZINC1603176-7WI-4C4Y, Diuron

Abstract

Structure-based drug design (SBDD) is a powerful and widely used approach to optimize affinity of drug candidates. With the recently introduced INPHARMA method, the binding mode of small molecules to their protein target can be characterized even if no spectroscopic information about the protein is known. Here, we show that the combination of the spin-diffusion-based NMR methods INPHARMA, trNOE, and STD results in an accurate scoring function for docking modes and therefore determination of protein-ligand complex structures. Applications are shown on the model system protein kinase A and the drug targets glycogen phosphorylase and soluble epoxide hydrolase (sEH). Multiplexing of several ligands improves the reliability of the scoring function further. The new score allows in the case of sEH detecting two binding modes of the ligand in its binding site, which was corroborated by X-ray analysis.