View source for 4txl


==Crystal structure of uridine phosphorylase from Schistosoma mansoni in complex with uracil==
<StructureSection load='4txl' size='340' side='right'caption='[[4txl]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4txl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TXL 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]] 1.92&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URA:URACIL'>URA</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=4txl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4txl OCA], [https://pdbe.org/4txl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4txl RCSB], [https://www.ebi.ac.uk/pdbsum/4txl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4txl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UPPA_SCHMA UPPA_SCHMA] Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate (PubMed:26898674). The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis (Probable).<ref>PMID:26898674</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Reports of Schistosoma mansoni strains resistant to praziquantel, the only therapeutic strategy available for the treatment of schistosomiasis, have motivated the scientific community towards the search for new possible therapies. Biochemical characterization of the parasite's metabolism is an essential component for the rational development of new therapeutic alternatives. One of the so far uncharacterized enzymes is uridine phosphorylase (UP) (EC 2.4.2.3), for which the parasite genome presents two isoforms (SmUPa and SmUPb) that share 92% sequence identity. In this paper, we present crystal structures for SmUPa and SmUPb in their free states as well as bound to different ligands. This we have complemented by enzyme kinetic characterization and phylogenetic analyses. Both enzymes present an overall fold and active site structure similar to other known UPs. The kinetic analyses showed conclusively that SmUPa is a regular uridine phosphorylase but by contrast SmUPb presented no detectable activity. This is particularly noteworthy given the high level of sequence identity between the two isoforms and is probably the result of the significant differences observed for SmUPb in the vicinity of the active site itself, suggesting that it is not a UP at all. On the other hand, it was not possible to identify an alternative function for SmUPb, although our phylogenetic analyses and expression data suggest that SmUPb is still functional and plays a role in parasite metabolism. The unusual UPb isoform may open up new opportunities for understanding unique features of S. mansoni metabolism.

Analysis of two Schistosoma mansoni uridine phosphorylases isoforms suggests the emergence of a protein with a non-canonical function.,da Silva Neto AM, Torini de Souza JR, Romanelo L, Cassago A, Serrao VH, DeMarco R, Brandao-Neto J, Garratt RC, Pereira HD Biochimie. 2016 Feb 18. pii: S0300-9084(16)00050-X. doi:, 10.1016/j.biochi.2016.02.007. PMID:26898674<ref>PMID:26898674</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4txl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Uridine phosphorylase 3D structures|Uridine phosphorylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schistosoma mansoni]]
[[Category: Brandao-Neto J]]
[[Category: Cassago A]]
[[Category: DeMarco R]]
[[Category: Marinho A]]
[[Category: Pereira HM]]
[[Category: Romanello L]]
[[Category: Torini J]]