View source for 7bcz


==Structure of the 4'-phosphopantetheinyl transferase PcpS from Pseudomonas aeruginosa==
<StructureSection load='7bcz' size='340' side='right'caption='[[7bcz]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7bcz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BCZ 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=7bcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bcz OCA], [https://pdbe.org/7bcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bcz RCSB], [https://www.ebi.ac.uk/pdbsum/7bcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bcz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9I4H2_PSEAE Q9I4H2_PSEAE] Involved in the biosynthesis of the siderophore enterobactin (enterochelin), which is a macrocyclic trimeric lactone of N-(2,3-dihydroxybenzoyl)-serine. The serine trilactone serves as a scaffolding for the three catechol functionalities that provide hexadentate coordination for the tightly ligated iron(2+) atoms. Plays an essential role in the assembly of the enterobactin by catalyzing the transfer of the 4'-phosphopantetheine (Ppant) moiety from coenzyme A to the apo-domains of both EntB (ArCP domain) and EntF (PCP domain) to yield their holo-forms which make them competent for the activation of 2,3-dihydroxybenzoate (DHB) and L-serine, respectively.[ARBA:ARBA00003937]
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== Publication Abstract from PubMed ==
Owing to their role in activating enzymes essential for bacterial viability and pathogenicity, phosphopantetheinyl transferases represent novel and attractive drug targets. In this work, we examined the inhibitory effect of the aminido-urea 8918 compound against the phosphopantetheinyl transferases PptAb from Mycobacterium abscessus and PcpS from Pseudomonas aeruginosa, two pathogenic bacteria associated with cystic fibrosis and bronchiectasis, respectively. Compound 8918 exhibits inhibitory activity against PptAb but displays no activity against PcpS in vitro, while no antimicrobial activity against Mycobacterium abscessus or Pseudomonas aeruginosa could be detected. X-ray crystallographic analysis of 8918 bound to PptAb-CoA alone and in complex with an acyl carrier protein domain in addition to the crystal structure of PcpS in complex with CoA revealed the structural basis for the inhibition mechanism of PptAb by 8918 and its ineffectiveness against PcpS. Finally, in crystallo screening of potent inhibitors from the National Cancer Institute library identified a hydroxypyrimidinethione derivative that binds PptAb. Both compounds could serve as scaffolds for the future development of phosphopantetheinyl transferases inhibitors.

Phosphopantetheinyl transferase binding and inhibition by amidino-urea and hydroxypyrimidinethione compounds.,Carivenc C, Maveyraud L, Blanger C, Ballereau S, Roy-Camille C, Nguyen MC, Genisson Y, Guilhot C, Chalut C, Pedelacq JD, Mourey L Sci Rep. 2021 Sep 10;11(1):18042. doi: 10.1038/s41598-021-97197-4. PMID:34508141<ref>PMID:34508141</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7bcz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Carivenc C]]
[[Category: Mourey L]]
[[Category: Pedelacq JD]]