View source for 5jix


==PKG II's Carboxyl Terminal Cyclic Nucleotide Binding Domain (CNB-B) in a complex with 8-Br-cGMP==
<StructureSection load='5jix' size='340' side='right'caption='[[5jix]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jix]] 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=5JIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JIX 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]] 1.47&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6J7:2-AMINO-8-BROMO-9-[(2R,4AR,6R,7R,7AS)-2,7-DIHYDROXY-2-OXOTETRAHYDRO-2H,4H-2LAMBDA~5~-FURO[3,2-D][1,3,2]DIOXAPHOSPHININ-6-YL]-1,9-DIHYDRO-6H-PURIN-6-ONE'>6J7</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PE5:3,6,9,12,15,18,21,24-OCTAOXAHEXACOSAN-1-OL'>PE5</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=5jix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jix OCA], [https://pdbe.org/5jix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jix RCSB], [https://www.ebi.ac.uk/pdbsum/5jix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jix ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KGP2_HUMAN KGP2_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyclic GMP analogs, 8-Br, 8-pCPT, and PET-cGMP, have been widely used for characterizing cellular functions of cGMP-dependent protein kinase (PKG) I and II isotypes. However, interpreting results obtained using these analogs has been difficult due to their low isotype specificity. Additionally, each isotype has two binding sites with different cGMP affinities and analog selectivities, making understanding the molecular basis for isotype specificity of these compounds even more challenging. To determine isotype specificity of cGMP analogs and their structural basis, we generated the full-length regulatory domains of PKG I and II isotypes with each binding site disabled, determined their affinities for these analogs, and obtained cocrystal structures of both isotypes bound with cGMP analogs. Our affinity and activation measurements show that PET-cGMP is most selective for PKG I, whereas 8-pCPT-cGMP is most selective for PKG II. Our structures of cyclic nucleotide binding (CNB) domains reveal that the B site of PKG I is more open and forms a unique pi/pi interaction through Arg285 at beta4 with the PET moiety, whereas the A site of PKG II has a larger beta5/beta6 pocket that can better accommodate the bulky 8-pCPT moiety. Our structural and functional results explain the selectivity of these analogs for each PKG isotype and provide a starting point for the rational design of isotype selective activators.

Structural Basis of Analog Specificity in PKG I and II.,Campbell JC, Henning P, Franz E, Sankaran B, Herberg FW, Kim C ACS Chem Biol. 2017 Aug 22. doi: 10.1021/acschembio.7b00369. PMID:28793191<ref>PMID:28793191</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jix" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Campbell JC]]
[[Category: Kim CW]]