View source for 6dft


==Trypanosoma brucei deoxyhypusine synthase==
<StructureSection load='6dft' size='340' side='right'caption='[[6dft]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dft]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DFT 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]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=6dft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dft OCA], [https://pdbe.org/6dft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dft RCSB], [https://www.ebi.ac.uk/pdbsum/6dft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dft ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DHYSC_TRYB2 DHYSC_TRYB2] In association with the non-catalytic regulatory subunit DHSp, catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF5A precursor protein to form the intermediate deoxyhypusine residue. Regulates protein levels of its regulatory subunit DHSp. Required for cell growth and survival.<ref>PMID:23525104</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trypanosoma brucei is a neglected tropical disease endemic to Africa. The polyamine spermidine is essential for post-translational hypusine modification of eukaryotic initiation factor 5A (eIF5A), which is catalyzed by deoxyhypusine synthase (TbDHS). In trypanosomatids, deoxyhypusine synthase (DHS) activity is dependent on heterotetramer formation between two paralogs, DHSc and DHSp, both with minimal activity on their own due to missing catalytic residues. We determined the X-ray structure of TbDHS showing a single functional shared active site is formed at the DHSc/DHSp heterodimer interface, with deficiencies in one subunit complemented by the other. Each heterodimer contains two NAD(+) binding sites, one housed in the functional catalytic site and the second bound in a remnant dead site that lacks key catalytic residues. Functional analysis of these sites by site-directed mutagenesis identified long-range contributions to the catalytic site from the dead site. Differences between trypanosomatid and human DHS that could be exploited for drug discovery were identified.

Trypanosomatid Deoxyhypusine Synthase Activity Is Dependent on Shared Active-Site Complementation between Pseudoenzyme Paralogs.,Afanador GA, Tomchick DR, Phillips MA Structure. 2018 Nov 6;26(11):1499-1512.e5. doi: 10.1016/j.str.2018.07.012. Epub, 2018 Sep 6. PMID:30197036<ref>PMID:30197036</ref>

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

==See Also==
*[[Deoxyhypusine synthase|Deoxyhypusine synthase]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei]]
[[Category: Afanador GA]]
[[Category: Phillips MA]]
[[Category: Tomchick DR]]