4C4Y

Crystal structure of human bifunctional epoxide hydroxylase 2 complexed with A4

Summary for 4C4Y

• Entry DOI: 10.2210/pdb4c4y/pdb
• Related: 4C4X 4C4Z
• Descriptor: BIFUNCTIONAL EPOXIDE HYDROLASE 2, 1-(3-chlorophenyl)-3-(2-methoxyethyl)urea (3 entities in total)
• Functional Keywords: hydrolase, drug design
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 37599.60

Authors

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. (deposition date: 2013-09-09, release date: 2014-10-01, Last modification date: 2023-12-20)

Primary citation

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, K.,Becker, S.,Griesinger, C.
A Combination of Spin Diffusion Methods for the Determination of Protein-Ligand Complex Structural Ensembles.
Angew.Chem.Int.Ed.Engl., 54:6511-, 2015

PubMed 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.

PubMed: 25877959
DOI: 10.1002/ANIE.201500671

Experimental method

X-RAY DIFFRACTION (2.41 Å)