View source for 6w3z


==Crystal Structure of Brugia malayi Deoxyhypusine synthase (DHPS)==
<StructureSection load='6w3z' size='340' side='right'caption='[[6w3z]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6w3z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Brugia_malayi Brugia malayi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W3Z 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=6w3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w3z OCA], [https://pdbe.org/6w3z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w3z RCSB], [https://www.ebi.ac.uk/pdbsum/6w3z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w3z ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0J9XTC4_BRUMA A0A0J9XTC4_BRUMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Deoxyhypusine synthase (DHS) catalyzes the first step of the post-translational modification of eukaryotic translation factor 5A (eIF5A), which is the only known protein containing the amino acid hypusine. Both proteins are essential for eukaryotic cell viability, and DHS has been suggested as a good candidate target for small molecule-based therapies against eukaryotic pathogens. In this work, we focused on the DHS enzymes from Brugia malayi and Leishmania major, the causative agents of lymphatic filariasis and cutaneous leishmaniasis, respectively. To enable B. malayi (Bm)DHS for future target-based drug discovery programs, we determined its crystal structure bound to cofactor NAD+. We also reported an in vitro biochemical assay for this enzyme that is amenable to a high-throughput screening format. The L. major genome encodes two DHS paralogs, and attempts to produce them recombinantly in bacterial cells were not successful. Nevertheless, we showed that ectopic expression of both LmDHS paralogs can rescue yeast cells lacking the endogenous DHS-encoding gene (dys1). Thus, functionally complemented dys1Delta yeast mutants can be used to screen for new inhibitors of the L. major enzyme. We used the known human DHS inhibitor GC7 to validate both in vitro and yeast-based DHS assays. Our results show that BmDHS is a homotetrameric enzyme that shares many features with its human homologue, whereas LmDHS paralogs are likely to form a heterotetrameric complex and have a distinct regulatory mechanism. We expect our work to facilitate the identification and development of new DHS inhibitors that can be used to validate these enzymes as vulnerable targets for therapeutic interventions against B. malayi and L. major infections.

Structural features and development of an assay platform of the parasite target deoxyhypusine synthase of Brugia malayi and Leishmania major.,Silva SF, Klippel AH, Ramos PZ, Santiago ADS, Valentini SR, Bengtson MH, Massirer KB, Bilsland E, Counago RM, Zanelli CF PLoS Negl Trop Dis. 2020 Oct 12;14(10):e0008762. doi:, 10.1371/journal.pntd.0008762. eCollection 2020 Oct. PMID:33044977<ref>PMID:33044977</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6w3z" style="background-color:#fffaf0;"></div>

==See Also==
*[[Deoxyhypusine synthase|Deoxyhypusine synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Brugia malayi]]
[[Category: Large Structures]]
[[Category: Arruda P]]
[[Category: Counago RM]]
[[Category: Edwards AM]]
[[Category: Klippel HA]]
[[Category: Massirer KB]]
[[Category: Ramos PZ]]
[[Category: Santiago AS]]
[[Category: Silva SF]]
[[Category: Zanelli CF]]
[[Category: Dos Reis CV]]