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==Structure of PDE5 PDE6 chimera==
<StructureSection load='10oz' size='340' side='right'caption='[[10oz]], [[Resolution|resolution]] 3.06&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[10oz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=10OZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=10OZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.06&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PCG:CYCLIC+GUANOSINE+MONOPHOSPHATE'>PCG</scene>, <scene name='pdbligand=VIA:5-{2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]PHENYL}-1-METHYL-3-PROPYL-1H,6H,7H-PYRAZOLO[4,3-D]PYRIMIDIN-7-ONE'>VIA</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=10oz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=10oz OCA], [https://pdbe.org/10oz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=10oz RCSB], [https://www.ebi.ac.uk/pdbsum/10oz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=10oz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PDE5A_BOVIN PDE5A_BOVIN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:8530505). Specifically regulates nitric-oxide-generated cGMP (By similarity).[UniProtKB:O76074]<ref>PMID:8530505</ref> [https://www.uniprot.org/uniprot/PDE6C_BOVIN PDE6C_BOVIN] As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.[UniProtKB:P51160]
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== Publication Abstract from PubMed ==
Phosphodiesterase 5 (PDE5) plays critical role in the nitric oxide-cGMP signaling pathway. Consequently, PDE5 catalytic site inhibitors are widely used in the treatment of erectile dysfunction and pulmonary arterial hypertension. Despite a wealth of structural data on the individual PDE5 catalytic domain with bound drug molecules, understanding of the structural organization of the full-length enzyme and its allosteric activation by noncatalytic cGMP-binding is lacking. To begin to understand the structural organization of PDE5, we solved a cryo-EM structure of a chimeric PDE enzyme (PDE6C/5) comprised of the regulatory domains of cone PDE6C and the PDE5 catalytic domain. The PDE6C/5 structure revealed the protein in the open state conformation similar to that of PDE6, suggesting a comparable conformation for the cGMP-bound PDE5 molecule. The H- and M-loops outlying the catalytic pocket, which are conformationally variable in the structures of isolated PDE5 catalytic domain, are immobilized in the PDE6/5 chimera via the interaction of the H-loop with a linker helix LH2. Decreased dynamics of these loops may underlie the higher catalytic activities of the full-length PDE5 and PDE6C/5 compared to that of the isolated PDE5 catalytic domain. Furthermore, the PDE6C/5 structure defines the folding requirement of the PDE6 catalytic domain for chaperone-dependent maturation that is important for vision.

Structural basis of phosphodiesterase-5 conformational organization revealed by a PDE6/PDE5 Chimera.,Srivastava D, Singh S, Yu C, Boyd K, Artemyev NO J Biol Chem. 2026 Apr 17:111467. doi: 10.1016/j.jbc.2026.111467. PMID:42001945<ref>PMID:42001945</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Artemyev NO]]
[[Category: Singh S]]
[[Category: Srivastava D]]