View source for 6rrp


==Crystal structure of tyrosinase PvdP from Pseudomonas aeruginosa bound to copper and phenylthiourea==
<StructureSection load='6rrp' size='340' side='right'caption='[[6rrp]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rrp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RRP 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=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=URS:N-PHENYLTHIOUREA'>URS</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=6rrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rrp OCA], [https://pdbe.org/6rrp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rrp RCSB], [https://www.ebi.ac.uk/pdbsum/6rrp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rrp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9I188_PSEAE Q9I188_PSEAE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The biosynthesis of pyoverdine, the major siderophore of Pseudomonas aeruginosa, is a well-organized process involving a discrete number of enzyme-catalyzed steps. The final step of this process involves the PvdP tyrosinase, which converts ferribactin into pyoverdine. Thus, inhibition of the PvdP tyrosinase activity provides an attractive strategy to interfere with siderophore synthesis to manage P. aeruginosa infections. Here, we report phenylthiourea as a non-competitive inhibitor of PvdP for which we solved a crystal structure in complex with PvdP. The crystal structure indicates that phenylthiourea binds to an allosteric binding site and thereby interferes with its tyrosinase activity. We further provide proofs that PvdP tyrosinase inhibition by phenylthiourea requires the C-terminal lid region. This provides opportunities to develop inhibitors that target the allosteric site, which seems to be confined to fluorescent pseudomonads, and not the tyrosinase active site. Furthermore, increases the chances to identify PvdP inhibitors that selectively interfere with siderophore synthesis.

A novel mechanism of inhibition by phenylthiourea on PvdP, a tyrosinase synthesizing pyoverdine of Pseudomonas aeruginosa.,Wibowo JP, Batista FA, van Oosterwijk N, Groves MR, Dekker FJ, Quax WJ Int J Biol Macromol. 2020 Mar 1;146:212-221. doi: 10.1016/j.ijbiomac.2019.12.252., Epub 2019 Dec 30. PMID:31899238<ref>PMID:31899238</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rrp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tyrosinase 3D structures|Tyrosinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa PAO1]]
[[Category: Batista FA]]
[[Category: Dekker FJ]]
[[Category: Groves MR]]
[[Category: Quax WJ]]
[[Category: Wibowo JP]]
[[Category: Van Oosterwijk N]]