4myq: Difference between revisions

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-{{STRUCTURE_4myq|  PDB=4myq  |  SCENE=  }}
-===Selective Inhibition of the Catalytic Domain Of Human Phosphodiesterase 4B With A-33===
-{{ABSTRACT_PUBMED_24361374}}
-==Function==
+==Selective Inhibition of the Catalytic Domain Of Human Phosphodiesterase 4B With A-33==
-[[http://www.uniprot.org/uniprot/PDE4B_HUMAN 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.<ref>PMID:10846163</ref> <ref>PMID:15003452</ref>
+<StructureSection load='4myq' size='340' side='right'caption='[[4myq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4myq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MYQ FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=19T:(4-{[2-(5-CHLOROTHIOPHEN-2-YL)-5-ETHYL-6-METHYLPYRIMIDIN-4-YL]AMINO}PHENYL)ACETIC+ACID'>19T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4myq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4myq OCA], [https://pdbe.org/4myq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4myq RCSB], [https://www.ebi.ac.uk/pdbsum/4myq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4myq ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PDE4B_HUMAN 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.<ref>PMID:10846163</ref> <ref>PMID:15003452</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Phosphodiesterase-4B (PDE4B) regulates the pro-inflammatory Toll Receptor -Tumor Necrosis Factor alpha (TNFalpha) pathway in monocytes, macrophages and microglial cells. As such, it is an important, although under-exploited molecular target for anti-inflammatory drugs. This is due in part to the difficulty of developing selective PDE4B inhibitors as the amino acid sequence of the PDE4 active site is identical in all PDE4 subtypes (PDE4A-D). We show that highly selective PDE4B inhibitors can be designed by exploiting sequence differences outside the active site. Specifically, PDE4B selectivity can be achieved by capture of a C-terminal regulatory helix, now termed CR3 (Control Region 3), across the active site in a conformation that closes access by cAMP. PDE4B selectivity is driven by a single amino acid polymorphism in CR3 (Leu674 in PDE4B1 versus Gln594 in PDE4D). The reciprocal mutations in PDE4B and PDE4D cause a 70-80 fold shift in selectivity. Our structural studies show that CR3 is flexible and can adopt multiple orientations and multiple registries in the closed conformation. The new co-crystal structure with bound ligand provides a guide map for the design of PDE4B selective anti-inflammatory drugs.
-==About this Structure==
+Structural basis for the design of selective phosphodiesterase 4B inhibitors.,Fox D 3rd, Burgin AB, Gurney ME Cell Signal. 2013 Dec 19;26(3):657-663. doi: 10.1016/j.cellsig.2013.12.003. PMID:24361374<ref>PMID:24361374</ref>
-[[4myq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MYQ OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:024361374</ref><references group="xtra"/><references/>
+</div>
-[[Category: 3',5'-cyclic-nucleotide phosphodiesterase]]
+<div class="pdbe-citations 4myq" style="background-color:#fffaf0;"></div>
-[[Category: Edwards, T E.]]
-[[Category: III, D Fox.]]
+==See Also==
-[[Category: Catalytic]]
+*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
-[[Category: Hydrolase]]
+== References ==
-[[Category: Hydrolase-hydrolase inhibitor complex]]
+<references/>
-[[Category: Phosphodiesterase]]
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Edwards TE]]
+[[Category: Fox III D]]