3SL8

Crystal structure of the catalytic domain of PDE4D2 with compound 10o

Summary for 3SL8

• Entry DOI: 10.2210/pdb3sl8/pdb
• Related: 1PTW 3SL3 3SL4 3SL5 3SL6
• Descriptor: cAMP-specific 3',5'-cyclic phosphodiesterase 4D, 1,2-ETHANEDIOL, ZINC ION, ... (8 entities in total)
• Functional Keywords: catalytic mechanism, camp hydrolysis, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Apical cell membrane : Q08499
• Total number of polymer chains: 4
• Total formula weight: 170881.57

Authors

Feil, S.F. (deposition date: 2011-06-24, release date: 2011-10-26, Last modification date: 2024-02-28)

Primary citation

Nankervis, J.L.,Feil, S.C.,Hancock, N.C.,Zheng, Z.,Ng, H.L.,Morton, C.J.,Holien, J.K.,Ho, P.W.,Frazzetto, M.M.,Jennings, I.G.,Manallack, D.T.,Martin, T.J.,Thompson, P.E.,Parker, M.W.
Thiophene inhibitors of PDE4: Crystal structures show a second binding mode at the catalytic domain of PDE4D2.
Bioorg.Med.Chem.Lett., 21:7089-7093, 2011

PubMed Abstract: PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor.

PubMed: 22030030
DOI: 10.1016/j.bmcl.2011.09.109

Experimental method

X-RAY DIFFRACTION (2.6 Å)