6oho: Difference between revisions
New page: '''Unreleased structure''' The entry 6oho is ON HOLD Authors: Metrick, C.M., Chodaparambil, J.V. Description: Structure of human Phospholipase D2 catalytic domain [[Category: Unrelease... |
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==Structure of human Phospholipase D2 catalytic domain== | |||
<StructureSection load='6oho' size='340' side='right'caption='[[6oho]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<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='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='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='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> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:32042197</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Chodaparambil | <div class="pdbe-citations 6oho" style="background-color:#fffaf0;"></div> | ||
[[Category: Metrick | |||
==See Also== | |||
*[[Phospholipase D 3D structures|Phospholipase D 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chodaparambil JV]] | |||
[[Category: Metrick CM]] | |||
Latest revision as of 10:10, 11 October 2023
Structure of human Phospholipase D2 catalytic domainStructure of human Phospholipase D2 catalytic domain
Structural highlights
FunctionPLD2_HUMAN May have a role in signal-induced cytoskeletal regulation and/or endocytosis. Publication Abstract from PubMedPhospholipase 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 AlsoReferences
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