6boj
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6boj' size='340' side='right' caption='[[6boj]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='6boj' size='340' side='right' caption='[[6boj]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6boj]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BOJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BOJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6boj]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BOJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BOJ FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E31:2-(4-{[2-(3-chlorophenyl)-6-ethylpyrimidin-4-yl]methyl}phenyl)acetamide'>E31</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E31:2-(4-{[2-(3-chlorophenyl)-6-ethylpyrimidin-4-yl]methyl}phenyl)acetamide'>E31</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDE4D, DPDE3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6boj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6boj OCA], [http://pdbe.org/6boj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6boj RCSB], [http://www.ebi.ac.uk/pdbsum/6boj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6boj ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6boj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6boj OCA], [http://pdbe.org/6boj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6boj RCSB], [http://www.ebi.ac.uk/pdbsum/6boj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6boj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 11: | Line 12: | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref> | [[http://www.uniprot.org/uniprot/PDE4D_HUMAN PDE4D_HUMAN]] Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.<ref>PMID:15260978</ref> <ref>PMID:15576036</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Inhibitors of phosphodiesterase-4 (PDE4) have beneficial effects on memory in preclinical and clinical studies. Development of these drugs has stalled due to dose-limiting side effects of nausea and emesis. While use of subtype-selective inhibitors (i.e., for PDE4A, B, or D) could overcome this issue, conservation of the catalytic region, to which classical inhibitors bind, limits this approach. The present study examined the effects of BPN14770, an allosteric inhibitor of PDE4D, which binds to a primate-specific, N-terminal region. In mice engineered to express PDE4D with this primate-specific sequence, BPN14770 was 100-fold more potent for improving memory than in wild-type mice; meanwhile, it exhibited low potency in a mouse surrogate model for emesis. BPN14770 also antagonized the amnesic effects of scopolamine, increased cAMP signaling in brain, and increased BDNF and markers of neuronal plasticity associated with memory. These data establish a relationship between PDE4D target engagement and effects on memory for BPN14770 and suggest clinical potential for PDE4D-selective inhibitors. | ||
| + | |||
| + | Memory enhancing effects of BPN14770, an allosteric inhibitor of phosphodiesterase-4D, in wild-type and humanized mice.,Zhang C, Xu Y, Chowdhary A, Fox D 3rd, Gurney ME, Zhang HT, Auerbach BD, Salvi RJ, Yang M, Li G, O'Donnell JM Neuropsychopharmacology. 2018 Aug 14. pii: 10.1038/s41386-018-0178-6. doi:, 10.1038/s41386-018-0178-6. PMID:30131563<ref>PMID:30131563</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6boj" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Fairman, J W]] | [[Category: Fairman, J W]] | ||
[[Category: Gurney, M E]] | [[Category: Gurney, M E]] | ||
Revision as of 10:25, 5 September 2018
Crystal Structure of the PDE4D Catalytic Domain and UCR2 Regulatory Helix with BPN5004
| |||||||||||
