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| | <StructureSection load='6u8z' size='340' side='right'caption='[[6u8z]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='6u8z' size='340' side='right'caption='[[6u8z]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6u8z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U8Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U8Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6u8z]] 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=6U8Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U8Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</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]] 1.799Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipase_D Phospholipase D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.4 3.1.4.4] </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=6u8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8z OCA], [https://pdbe.org/6u8z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u8z RCSB], [https://www.ebi.ac.uk/pdbsum/6u8z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8z ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6u8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8z OCA], [http://pdbe.org/6u8z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u8z RCSB], [http://www.ebi.ac.uk/pdbsum/6u8z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PLD1_HUMAN PLD1_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/PLD1_HUMAN PLD1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLD1_HUMAN PLD1_HUMAN]] Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity). | + | [https://www.uniprot.org/uniprot/PLD1_HUMAN PLD1_HUMAN] Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6u8z" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6u8z" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phospholipase D 3D structures|Phospholipase D 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phospholipase D]]
| + | [[Category: Airola MV]] |
| - | [[Category: Airola, M V]] | + | [[Category: Bowling FZ]] |
| - | [[Category: Bowling, F Z]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphohistidine]]
| + | |
| - | [[Category: Phospholipase d1]]
| + | |
| - | [[Category: Pip2 binding]]
| + | |
| - | [[Category: Pld]]
| + | |
| Structural highlights
Disease
PLD1_HUMAN The disease is caused by mutations affecting the gene represented in this entry.
Function
PLD1_HUMAN Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity).
Publication Abstract from PubMed
The signal transduction enzyme phospholipase D1 (PLD1) hydrolyzes phosphatidylcholine to generate the lipid second-messenger phosphatidic acid, which plays roles in disease processes such as thrombosis and cancer. PLD1 is directly and synergistically regulated by protein kinase C, Arf and Rho GTPases, and the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2). Here, we present a 1.8 A-resolution crystal structure of the human PLD1 catalytic domain, which is characterized by a globular fold with a funnel-shaped hydrophobic cavity leading to the active site. Adjacent is a PIP2-binding polybasic pocket at the membrane interface that is essential for activity. The C terminus folds into and contributes part of the catalytic pocket, which harbors a phosphohistidine that mimics an intermediate stage of the catalytic cycle. Mapping of PLD1 mutations that disrupt RhoA activation identifies the RhoA-PLD1 binding interface. This structure sheds light on PLD1 regulation by lipid and protein effectors, enabling rationale inhibitor design for this well-studied therapeutic target.
Crystal structure of human PLD1 provides insight into activation by PI(4,5)P2 and RhoA.,Bowling FZ, Salazar CM, Bell JA, Huq TS, Frohman MA, Airola MV Nat Chem Biol. 2020 Apr;16(4):400-407. doi: 10.1038/s41589-020-0499-8. Epub 2020 , Mar 16. PMID:32198492[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bowling FZ, Salazar CM, Bell JA, Huq TS, Frohman MA, Airola MV. Crystal structure of human PLD1 provides insight into activation by PI(4,5)P2 and RhoA. Nat Chem Biol. 2020 Apr;16(4):400-407. doi: 10.1038/s41589-020-0499-8. Epub 2020 , Mar 16. PMID:32198492 doi:http://dx.doi.org/10.1038/s41589-020-0499-8
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