8v5t

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Current revision (07:02, 9 October 2024) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8v5t is ON HOLD until Paper Publication
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==Crystal structure of Alzheimers disease phospholipase D3==
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<StructureSection load='8v5t' size='340' side='right'caption='[[8v5t]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8v5t]] 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=8V5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8V5T FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8v5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8v5t OCA], [https://pdbe.org/8v5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8v5t RCSB], [https://www.ebi.ac.uk/pdbsum/8v5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8v5t ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PLD3_HUMAN PLD3_HUMAN] Spinocerebellar ataxia type 46. The disease may be caused by variants affecting the gene represented in this entry. There is limited evidences for implication of PLD3 in SCA46. Knockout mice do not present signs of cerebellar degeneration or spinocerebellar ataxia at 9 months of age, challenging the interpretation of the suggested loss-of-function mechanism for PLD3 as the SCA46-causative gene.<ref>PMID:30312375</ref> Genetic variants in PLD3 have been suggested to be associated with an increased risk for Alzheimer disease (PubMed:24336208, PubMed:25832409). Further studies, however, did not support PLD3 involvement in this disease (PubMed:25832408, PubMed:25832410, PubMed:25832411, PubMed:25832413, PubMed:26411346). Futhermore, it is controversial whether PLD3 plays a role in amyloid precursor protein processing (APP) or not (PubMed:24336208). In a relevant Alzheimer's disease mouse model PLD3 deficiency does not affect APP metabolism or amyloid plaque burden (PubMed:28128235). However one study shown that PLD3 influences APP processing (PubMed:24336208).<ref>PMID:24336208</ref> <ref>PMID:25832408</ref> <ref>PMID:25832409</ref> <ref>PMID:25832410</ref> <ref>PMID:25832411</ref> <ref>PMID:25832413</ref> <ref>PMID:26411346</ref> <ref>PMID:28128235</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PLD3_HUMAN PLD3_HUMAN] 5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA) (PubMed:30312375). Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor in collaboration with PLD4 (By similarity). May be important in myotube formation (PubMed:22428023). Plays a role in lysosomal homeostasis (PubMed:28128235). Involved in the regulation of endosomal protein sorting (PubMed:29368044).[UniProtKB:O35405]<ref>PMID:22428023</ref> <ref>PMID:28128235</ref> <ref>PMID:29368044</ref> <ref>PMID:30312375</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human 5'-3' exonuclease PLD3, a member of the phospholipase D family of enzymes, has been validated as a therapeutic target for treating Alzheimer's disease. Here, we have determined the crystal structure of the luminal domain of the enzyme at 2.3 A resolution, revealing a bilobal structure with a catalytic site located between the lobes. We then compared the structure with published crystal structures of other human PLD family members which revealed that a number of catalytic and lipid recognition residues, previously shown to be key for phospholipase activity, are not conserved or, are absent. This led us to test whether the enzyme is actually a phospholipase. We could not measure any phospholipase activity but the enzyme shows robust nuclease activity. Finally, we have mapped key single nucleotide polymorphisms onto the structure which reveals plausible reasons as to why they have an impact on Alzheimer's disease.
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Authors:
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Crystal structure of Alzheimer's disease phospholipase D3 provides a molecular basis for understanding its normal and pathological functions.,Ishii K, Hermans SJ, Georgopoulou ME, Nero TL, Hancock NC, Crespi GAN, Gorman MA, Gooi JH, Parker MW FEBS J. 2024 Sep 26. doi: 10.1111/febs.17277. PMID:39325669<ref>PMID:39325669</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8v5t" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Gorman MA]]
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[[Category: Hermans SJ]]
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[[Category: Ishii K]]
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[[Category: Nero TL]]
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[[Category: Parker MW]]

Current revision

Crystal structure of Alzheimers disease phospholipase D3

PDB ID 8v5t

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