View source for 7drk


==Crystal structure of phosphatidylglycerol phosphate synthase in complex with cytidine diphosphate-diacylglycerol==
<StructureSection load='7drk' size='340' side='right'caption='[[7drk]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7drk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DRK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DRK 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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=58A:5-O-[(R)-{[(S)-{(2R)-2,3-BIS[(9E)-OCTADEC-9-ENOYLOXY]PROPOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]CYTIDINE'>58A</scene>, <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</scene>, <scene name='pdbligand=G3P:SN-GLYCEROL-3-PHOSPHATE'>G3P</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7drk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7drk OCA], [https://pdbe.org/7drk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7drk RCSB], [https://www.ebi.ac.uk/pdbsum/7drk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7drk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PGSA_STAAN PGSA_STAAN] This protein catalyzes the committed step to the synthesis of the acidic phospholipids.
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== Publication Abstract from PubMed ==
Phosphatidylglycerol is a crucial phospholipid found ubiquitously in biological membranes of prokaryotic and eukaryotic cells. The phosphatidylglycerol phosphate (PGP) synthase (PgsA), a membrane-embedded enzyme, catalyzes the primary reaction of phosphatidylglycerol biosynthesis. Mutations in pgsA frequently correlate with daptomycin resistance in Staphylococcus aureus and other prevalent infectious pathogens. Here we report the crystal structures of S. aureus PgsA (SaPgsA) captured at two distinct states of the catalytic process, with lipid substrate (cytidine diphosphate-diacylglycerol, CDP-DAG) or product (PGP) bound to the active site within a trifurcated amphipathic cavity. The hydrophilic head groups of CDP-DAG and PGP occupy two different pockets in the cavity, inducing local conformational changes. An elongated membrane-exposed surface groove accommodates the fatty acyl chains of CDP-DAG/PGP and opens a lateral portal for lipid entry/release. Remarkably, the daptomycin resistance-related mutations mostly cluster around the active site, causing reduction of enzymatic activity. Our results provide detailed mechanistic insights into the dynamic catalytic process of PgsA and structural frameworks beneficial for development of antimicrobial agents targeting PgsA from pathogenic bacteria.

The phosphatidylglycerol phosphate synthase PgsA utilizes a trifurcated amphipathic cavity for catalysis at the membrane-cytosol interface.,Yang B, Yao H, Li D, Liu Z Curr Res Struct Biol. 2021 Nov 23;3:312-323. doi: 10.1016/j.crstbi.2021.11.005., eCollection 2021. PMID:34901881<ref>PMID:34901881</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7drk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus subsp. aureus N315]]
[[Category: Liu ZF]]
[[Category: Yang BW]]