4nw7

PDE4 catalytic domainPDE4 catalytic domain

Structural highlights 4nw7 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PDE4B_HUMAN Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. Publication Abstract from PubMed In this study we report a series of triazine derivatives that are potent inhibitors of PDE4B. We also provide a series of structure activity relationships that demonstrate the triazine core can be used to generate subtype selective inhibitors of PDE4B versus PDE4D. A high resolution co-crystal structure shows that the inhibitors interact with a C-terminal regulatory helix (CR3) locking the enzyme in an inactive 'closed' conformation. The results show that the compounds interact with both catalytic domain and CR3 residues. This provides the first structure-based approach to engineer PDE4B-selective inhibitors. Discovery of triazines as selective PDE4B versus PDE4D inhibitors.,Hagen TJ, Mo X, Burgin AB, Fox D 3rd, Zhang Z, Gurney ME Bioorg Med Chem Lett. 2014 Aug 15;24(16):4031-4. doi: 10.1016/j.bmcl.2014.06.002., Epub 2014 Jun 12. PMID:24998378 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase 3D structures

spinqualitylabelsall models 4nw7, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image