View source for 8a25


==Lysophospholipase PlaA from Legionella pneumophila str. Corby - complex with PEG fragment==
<StructureSection load='8a25' size='340' side='right'caption='[[8a25]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8a25]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_pneumophila_str._Corby Legionella pneumophila str. Corby]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A25 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]] 1.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=8a25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a25 OCA], [https://pdbe.org/8a25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a25 RCSB], [https://www.ebi.ac.uk/pdbsum/8a25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a25 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A378KFD4_LEGPN A0A378KFD4_LEGPN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Legionella pneumophila, the causative agent of a life-threatening pneumonia, intracellularly replicates in a specialized compartment in lung macrophages, the Legionella-containing vacuole (LCV). Secreted proteins of the pathogen govern important steps in the intracellular life cycle including bacterial egress. Among these is the type II secreted PlaA which, together with PlaC and PlaD, belongs to the GDSL phospholipase family found in L. pneumophila. PlaA shows lysophospholipase A (LPLA) activity which increases after secretion and subsequent processing by the zinc metalloproteinase ProA within a disulfide loop. Activity of PlaA contributes to the destabilization of the LCV in the absence of the type IVB-secreted effector SdhA. We here present the 3D structure of PlaA which shows a typical alpha/beta-hydrolase fold and reveals that the uncleaved disulfide loop forms a lid structure covering the catalytic triad S30/D278/H282. This leads to reduction of substrate access before activation; however, the catalytic site gets more accessible when the disulfide loop is processed. After structural modeling, a similar activation process is suggested for the GDSL hydrolase PlaC, but not for PlaD. Furthermore, the size of the PlaA substrate-binding site indicated preference toward phospholipids comprising ~16 carbon fatty acid residues which was verified by lipid hydrolysis, suggesting a molecular ruler mechanism. Indeed, mutational analysis changed the substrate profile with respect to fatty acid chain length. In conclusion, our analysis revealed the structural basis for the regulated activation and substrate preference of PlaA.

Structure-function relationships underpin disulfide loop cleavage-dependent activation of Legionella pneumophila lysophospholipase A PlaA.,Hiller M, Diwo M, Wamp S, Gutsmann T, Lang C, Blankenfeldt W, Flieger A Mol Microbiol. 2024 Mar;121(3):497-512. doi: 10.1111/mmi.15201. Epub 2023 Dec 22. PMID:38130174<ref>PMID:38130174</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8a25" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Legionella pneumophila str. Corby]]
[[Category: Blankenfeldt W]]
[[Category: Diwo MG]]