View source for 9fxq


==Ancestral Prenylcysteine Oxidase 1 (PCYOX1)==
<StructureSection load='9fxq' size='340' side='right'caption='[[9fxq]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fxq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mammalia Mammalia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FXQ 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPS:3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE'>CPS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=9fxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fxq OCA], [https://pdbe.org/9fxq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fxq RCSB], [https://www.ebi.ac.uk/pdbsum/9fxq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fxq ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Prenylcysteine oxidases (PCYOXs) metabolize prenylated cysteines produced by protein degradation. They utilize oxygen as co-substrate to produce free cysteine, an aldehyde, and hydrogen peroxide through the unusual oxidation of a thioether bond. In this study, we explore the evolution, structure, and mechanism of the two mammalian PCYOXs. A gene duplication event in jawed vertebrates originated these two paralogs. Both enzymes are active on farnesyl- and geranylgeranylcysteine, but inactive on molecules with shorter prenyl groups. Kinetics experiments outline a mechanism where flavin reduction and re-oxidation occur rapidly without any detectable intermediates, with the overall reaction rate limited by product release. The experimentally determined three-dimensional structure of PCYOX1 reveals long and wide tunnels leading from the surface to the flavin. They allow the isoprene substrate to curl up within the protein and position its reactive cysteine group close to the flavin. A hydrophobic patch on the surface mediates membrane association, enabling direct substrate and product exchange with the lipid bilayer. Leveraging established knowledge on flavoenzyme inhibition, we designed sub-micromolar PCYOX inhibitors. Additionally, we discovered that PCYOXs bind and slowly degrade salisirab, an anti-RAS compound. This activity suggests potential and previously unknown roles of PCYOXs in drug metabolism.

Evolution, Structure, and Drug-Metabolising Activity of Mammalian Prenylcysteine Oxidases.,Barone M, Pizzorni L, Fraaije MW, Mascotti ML, Mattevi A J Biol Chem. 2024 Sep 23:107810. doi: 10.1016/j.jbc.2024.107810. PMID:39322016<ref>PMID:39322016</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9fxq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mammalia]]
[[Category: Barone M]]
[[Category: Mattevi A]]