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| | <StructureSection load='6oho' size='340' side='right'caption='[[6oho]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6oho' size='340' side='right'caption='[[6oho]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6oho]] is a 2 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=6OHO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OHO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6oho]] 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=6OHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OHO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLD2 ([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=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6oho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oho OCA], [https://pdbe.org/6oho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oho RCSB], [https://www.ebi.ac.uk/pdbsum/6oho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oho 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=6oho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oho OCA], [http://pdbe.org/6oho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oho RCSB], [http://www.ebi.ac.uk/pdbsum/6oho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oho ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLD2_HUMAN PLD2_HUMAN]] May have a role in signal-induced cytoskeletal regulation and/or endocytosis. | + | [https://www.uniprot.org/uniprot/PLD2_HUMAN PLD2_HUMAN] May have a role in signal-induced cytoskeletal regulation and/or endocytosis. |
| | <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 6oho" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6oho" 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: Chodaparambil JV]] |
| - | [[Category: Chodaparambil, J V]] | + | [[Category: Metrick CM]] |
| - | [[Category: Metrick, C M]] | + | |
| - | [[Category: Hkd motif]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphodiesterase]]
| + | |
| Structural highlights
Function
PLD2_HUMAN May have a role in signal-induced cytoskeletal regulation and/or endocytosis.
Publication Abstract from PubMed
Phospholipase D enzymes (PLDs) are ubiquitous phosphodiesterases that produce phosphatidic acid (PA), a key second messenger and biosynthetic building block. Although an orthologous bacterial Streptomyces sp. strain PMF PLD structure was solved two decades ago, the molecular basis underlying the functions of the human PLD enzymes (hPLD) remained unclear based on this structure due to the low homology between these sequences. Here, we describe the first crystal structures of hPLD1 and hPLD2 catalytic domains and identify novel structural elements and functional differences between the prokaryotic and eukaryotic enzymes. Furthermore, structure-based mutation studies and structures of inhibitor-hPLD complexes allowed us to elucidate the binding modes of dual and isoform-selective inhibitors, highlight key determinants of isoenzyme selectivity and provide a basis for further structure-based drug discovery and functional characterization of this therapeutically important superfamily of enzymes.
Human PLD structures enable drug design and characterization of isoenzyme selectivity.,Metrick CM, Peterson EA, Santoro JC, Enyedy IJ, Murugan P, Chen T, Michelsen K, Cullivan M, Spilker KA, Kumar PR, May-Dracka TL, Chodaparambil JV Nat Chem Biol. 2020 Feb 10. pii: 10.1038/s41589-019-0458-4. doi:, 10.1038/s41589-019-0458-4. PMID:32042197[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Metrick CM, Peterson EA, Santoro JC, Enyedy IJ, Murugan P, Chen T, Michelsen K, Cullivan M, Spilker KA, Kumar PR, May-Dracka TL, Chodaparambil JV. Human PLD structures enable drug design and characterization of isoenzyme selectivity. Nat Chem Biol. 2020 Feb 10. pii: 10.1038/s41589-019-0458-4. doi:, 10.1038/s41589-019-0458-4. PMID:32042197 doi:http://dx.doi.org/10.1038/s41589-019-0458-4
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