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2vcq

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2vcq, resolution 1.95Å ()
Ligands: ,
Activity: Prostaglandin-D synthase, with EC number 5.3.99.2
Related: 1v40, 1iyh, 1iyi
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

COMPLEX STRUCTURE OF PROSTAGLANDIN D2 SYNTHASE AT 1.95A.

Publication Abstract from PubMed

We describe the discovery of novel inhibitors of prostaglandin D2 synthase (PGDS) through fragment-based lead generation and structure-based drug design. A library of 2500 low-molecular-weight compounds was screened using 2D nuclear magnetic resonance (NMR), leading to the identification of 24 primary hits. Structure determination of protein-ligand complexes with the hits enabled a hit optimization process, whereby we harvested increasingly more potent inhibitors out of our corporate compound collection. Two iterative cycles were carried out, comprising NMR screening, molecular modeling, X-ray crystallography, and in vitro biochemical testing. Six novel high-resolution PGDS complex structures were determined, and 300 hit analogues were tested. This rational drug design procedure culminated in the discovery of 24 compounds with an IC 50 below 1 microM in the in vitro assay. The best inhibitor (IC 50 = 21 nM) is one of the most potent inhibitors of PGDS to date. As such, it may enable new functional in vivo studies of PGDS and the prostaglandin metabolism pathway.

Novel prostaglandin d synthase inhibitors generated by fragment-based drug design., Hohwy M, Spadola L, Lundquist B, Hawtin P, Dahmen J, Groth-Clausen I, Nilsson E, Persdotter S, von Wachenfeldt K, Folmer RH, Edman K, J Med Chem. 2008 Apr 10;51(7):2178-86. Epub 2008 Mar 15. PMID:18341273

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2vcq is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Hohwy M, Spadola L, Lundquist B, Hawtin P, Dahmen J, Groth-Clausen I, Nilsson E, Persdotter S, von Wachenfeldt K, Folmer RH, Edman K. Novel prostaglandin d synthase inhibitors generated by fragment-based drug design. J Med Chem. 2008 Apr 10;51(7):2178-86. Epub 2008 Mar 15. PMID:18341273 doi:http://dx.doi.org/10.1021/jm701509k

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