View source for 6fxw


==Structure of Leishmania infantum type B ribose 5-phosphate isomerase==
<StructureSection load='6fxw' size='340' side='right'caption='[[6fxw]], [[Resolution|resolution]] 1.57&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fxw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_infantum Leishmania infantum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FXW 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]] 1.57&#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></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=6fxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fxw OCA], [https://pdbe.org/6fxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fxw RCSB], [https://www.ebi.ac.uk/pdbsum/6fxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fxw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A4I3S4_LEIIN A4I3S4_LEIIN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Neglected tropical diseases caused by kinetoplastid parasites (Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp.) place a significant health and economic burden on developing nations worldwide. Current therapies are largely outdated, inadequate, and face mounting drug resistance from the causative parasites. Thus, there is an urgent need for drug discovery and development. Target-led drug discovery approaches have focused on the identification of parasite enzymes catalyzing essential biochemical processes, which significantly differ from equivalent proteins found in humans, thereby providing potentially exploitable therapeutic windows. One such target is ribose 5-phosphate isomerase B (RpiB), an enzyme involved in the nonoxidative branch of the pentose phosphate pathway, which catalyzes the interconversion of d-ribose 5-phosphate and d-ribulose 5-phosphate. Although protozoan RpiB has been the focus of numerous targeted studies, compounds capable of selectively inhibiting this parasite enzyme have not been identified. Here, we present the results of a fragment library screening against Leishmania infantum RpiB (LiRpiB), performed using thermal shift analysis. Hit fragments were shown to be effective inhibitors of LiRpiB in activity assays, and several fragments were capable of selectively inhibiting parasite growth in vitro. These results support the identification of LiRpiB as a validated therapeutic target. The X-ray crystal structure of apo LiRpiB was also solved, permitting docking studies to assess how hit fragments might interact with LiRpiB to inhibit its activity. Overall, this work will guide structure-based development of LiRpiB inhibitors as antileishmanial agents.

Toward Chemical Validation of Leishmania infantum Ribose 5-Phosphate Isomerase as a Drug Target.,Dickie EA, Ronin C, Sa M, Ciesielski F, Trouche N, Tavares J, Santarem N, Major LL, Pemberton IK, MacDougall J, Smith TK, Cordeiro-da-Silva A, Ciapetti P Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0189220. doi: , 10.1128/AAC.01892-20. Epub 2021 Jun 17. PMID:33875438<ref>PMID:33875438</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fxw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania infantum]]
[[Category: Ciapetti P]]
[[Category: Ciesielski F]]
[[Category: Ronin C]]