5AIS

Complex of human hematopoietic prostagandin D2 synthase (hH-PGDS) in complex with an active site inhibitor.

Summary for 5AIS

• Entry DOI: 10.2210/pdb5ais/pdb
• Related: 5AIV
• Descriptor: HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE, 4-(dimethylamino)-N-[5-(1H-indol-4-yl)pyridin-3-yl]butanamide, GLUTATHIONE, ... (5 entities in total)
• Functional Keywords: transferase, prostaglandin d2 synthase, pgds inhibitors, indole, focused screening, hit validation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : O60760
• Total number of polymer chains: 4
• Total formula weight: 96078.64

Authors

Edfeldt, F.,Evenas, J.,Lepisto, M.,Ward, A.,Petersen, J.,Wissler, L.,Rohman, M.,Sivars, U.,Svensson, K.,Perry, M.,Feierberg, I.,Zhou, X.,Hansson, T.,Narjes, F. (deposition date: 2015-02-17, release date: 2015-06-03, Last modification date: 2024-05-08)

Primary citation

Edfeldt, F.,Even, J.,Lepisto, M.,Ward, A.,Petersen, J.,Wissler, L.,Rohman, M.,Sivars, U.,Svensson, K.,Perry, M.,Feierberg, I.,Zhou, X.H.,Hansson, T.,Narjes, F.
Identification of Indole Inhibitors of Human Hematopoietic Prostaglandin D2 Synthase (Hh-Pgds).
Bioorg.Med.Chem.Lett., 25:2496-, 2015

PubMed Abstract: Human H-PGDS has shown promise as a potential target for anti-allergic and anti-inflammatory drugs. Here we describe the discovery of a novel class of indole inhibitors, identified through focused screening of 42,000 compounds and evaluated using a series of hit validation assays that included fluorescence polarization binding, 1D NMR, ITC and chromogenic enzymatic assays. Compounds with low nanomolar potency, favorable physico-chemical properties and inhibitory activity in human mast cells have been identified. In addition, our studies suggest that the active site of hH-PGDS can accommodate larger structural diversity than previously thought, such as the introduction of polar groups in the inner part of the binding pocket.

PubMed: 25978964
DOI: 10.1016/J.BMCL.2015.04.065

Experimental method

X-RAY DIFFRACTION (1.85 Å)