View source for 7lrd


==Cryo-EM of the SLFN12-PDE3A complex: Consensus subset model==
<StructureSection load='7lrd' size='340' side='right'caption='[[7lrd]], [[Resolution|resolution]] 3.22&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lrd]] is a 4 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=7LRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LRD 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]] 3.22&#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=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=X5M:(4~{R})-3-[4-(diethylamino)-3-[oxidanyl(oxidanylidene)-$l^{4}-azanyl]phenyl]-4-methyl-4,5-dihydro-1~{H}-pyridazin-6-one'>X5M</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=7lrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lrd OCA], [https://pdbe.org/7lrd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lrd RCSB], [https://www.ebi.ac.uk/pdbsum/7lrd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lrd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SLN12_HUMAN SLN12_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.

Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase.,Garvie CW, Wu X, Papanastasiou M, Lee S, Fuller J, Schnitzler GR, Horner SW, Baker A, Zhang T, Mullahoo JP, Westlake L, Hoyt SH, Toetzl M, Ranaghan MJ, de Waal L, McGaunn J, Kaplan B, Piccioni F, Yang X, Lange M, Tersteegen A, Raymond D, Lewis TA, Carr SA, Cherniack AD, Lemke CT, Meyerson M, Greulich H Nat Commun. 2021 Jul 16;12(1):4375. doi: 10.1038/s41467-021-24495-w. PMID:34272366<ref>PMID:34272366</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lrd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fuller JR]]
[[Category: Garvie CW]]
[[Category: Lemke CT]]