3EE2

Structure of human prostaglandin D-synthase (hGSTS1-1) in complex with nocodazole

Summary for 3EE2

• Entry DOI: 10.2210/pdb3ee2/pdb
• Related: 1IYH 1IYI 1PD2 1V40 2CVD
• Descriptor: Glutathione-requiring prostaglandin D synthase, GLUTATHIONE, nocodazole, ... (5 entities in total)
• Functional Keywords: h-pgds, prostanoid production, inflamation, nocodazole, glutathione transferase sigma, fatty acid biosynthesis, isomerase, lipid synthesis, prostaglandin biosynthesis
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : O60760
• Total number of polymer chains: 2
• Total formula weight: 47402.66

Authors

Oakley, A.J. (deposition date: 2008-09-04, release date: 2008-09-16, Last modification date: 2023-11-01)

Primary citation

Weber, J.E.,Oakley, A.J.,Christ, A.N.,Clark, A.G.,Hayes, J.D.,Hall, R.,Hume, D.A.,Board, P.G.,Smythe, M.L.,Flanagan, J.U.
Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D(2) synthase
Eur.J.Med.Chem., 45:447-454, 2010

PubMed Abstract: Prostaglandin D(2) synthesised by the hematopoietic prostaglandin D(2) synthase has a pro-inflammatory effect in allergic asthma, regulating many hallmark characteristics of the disease. Here we describe identification of hematopoietic prostaglandin D(2) synthase inhibitors including cibacron blue, bromosulfophthalein and ethacrynic acid. Expansion around the drug-like ethacrynic acid identified a novel inhibitor, nocodazole, and a fragment representing its aromatic core. Nocodazole binding was further characterised by docking calculations in combination with conformational strain analysis. The benzyl thiophene core was predicted to be buried in the active site, binding in the putative prostaglandin binding site, and a likely hydrogen bond donor site identified. X-ray crystallographic studies supported the predicted binding mode.

PubMed: 19939518
DOI: 10.1016/j.ejmech.2009.10.025

Experimental method

X-RAY DIFFRACTION (1.91 Å)