4EE0

Crystal structure of hH-PGDS with water displacing inhibitor

Summary for 4EE0

• Entry DOI: 10.2210/pdb4ee0/pdb
• Related: 4EDY 4EDZ
• Descriptor: Hematopoietic prostaglandin D synthase, MAGNESIUM ION, 4-(isoquinolin-1-yl)-N-[2-(morpholin-4-yl)ethyl]benzamide, ... (5 entities in total)
• Functional Keywords: inhibitor, solvent replacement, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O60760
• Total number of polymer chains: 2
• Total formula weight: 48181.39

Authors

Day, J.E.,Thorarensen, A.,Trujillo, J.I. (deposition date: 2012-03-28, release date: 2012-07-18, Last modification date: 2024-02-28)

Primary citation

Trujillo, J.I.,Kiefer, J.R.,Huang, W.,Day, J.E.,Moon, J.,Jerome, G.M.,Bono, C.P.,Kornmeier, C.M.,Williams, M.L.,Kuhn, C.,Rennie, G.R.,Wynn, T.A.,Carron, C.P.,Thorarensen, A.
Investigation of the binding pocket of human hematopoietic prostaglandin (PG) D2 synthase (hH-PGDS): a tale of two waters.
Bioorg.Med.Chem.Lett., 22:3795-3799, 2012

PubMed Abstract: The inhibition of hH-PGDS has been proposed as a potential target for the development of anti-allergic and anti-inflammatory drugs. Herein we describe our investigation of the binding pocket of this important enzyme and our observation that two water molecules bind to our inhibitors and the enzyme. A series of compounds were prepared to the probe the importance of the water molecules in determining the binding affinity of the inhibitors to the enzyme. The study provides insight into the binding requirements for the design of potent hH-PGDS inhibitors.

PubMed: 22546671
DOI: 10.1016/j.bmcl.2012.04.004

Experimental method

X-RAY DIFFRACTION (1.75 Å)