4x0f: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4x0f]] is a 2 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=4X0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X0F FirstGlance]. <br> | <table><tr><td colspan='2'>[[4x0f]] is a 2 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=4X0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X0F FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ROL:ROLIPRAM'>ROL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.22Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ROL:ROLIPRAM'>ROL</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=4x0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x0f OCA], [https://pdbe.org/4x0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x0f RCSB], [https://www.ebi.ac.uk/pdbsum/4x0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x0f ProSAT]</span></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=4x0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x0f OCA], [https://pdbe.org/4x0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x0f RCSB], [https://www.ebi.ac.uk/pdbsum/4x0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x0f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 10:39, 27 September 2023
Crystal structure of crosslink stabilized long-form PDE4B in complex with (R)-(-)-rolipramCrystal structure of crosslink stabilized long-form PDE4B in complex with (R)-(-)-rolipram
Structural highlights
FunctionPDE4B_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.[1] [2] Publication Abstract from PubMedPhosphodiesterase 4 (PDE4) is an essential contributor to intracellular signaling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain. Alternative promoters, transcriptional start sites, and mRNA splicing lead to the existence of over 25 variants of PDE4, broadly classified as long, short, and supershort forms. We report the X-ray crystal structure of long form PDE4B containing UCR1, UCR2, and the catalytic domain, crystallized as a dimer in which a disulfide bond cross-links cysteines engineered into UCR2 and the catalytic domain. Biochemical and mass spectrometric analyses showed that the UCR2-catalytic domain interaction occurs in trans, and established that this interaction regulates the catalytic activity of PDE4. By elucidating the key structural determinants of dimerization, we show that only long forms of PDE4 can be regulated by this mechanism. The results also provide a structural basis for the long-standing observation of high- and low-affinity binding sites for the prototypic inhibitor rolipram. Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4.,Cedervall P, Aulabaugh A, Geoghegan KF, McLellan TJ, Pandit J Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):E1414-22. doi:, 10.1073/pnas.1419906112. Epub 2015 Mar 9. PMID:25775568[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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