View source for 4zdl


==The crystal structure of the T325S mutant of the human holo SepSecS==
<StructureSection load='4zdl' size='340' side='right'caption='[[4zdl]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zdl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZDL 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]] 2.26&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=PLR:(5-HYDROXY-4,6-DIMETHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>PLR</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=4zdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zdl OCA], [https://pdbe.org/4zdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zdl RCSB], [https://www.ebi.ac.uk/pdbsum/4zdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zdl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPCS_HUMAN SPCS_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS-Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*-induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders.

Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase.,Puppala AK, French RL, Matthies D, Baxa U, Subramaniam S, Simonovic M Sci Rep. 2016 Aug 31;6:32563. doi: 10.1038/srep32563. PMID:27576344<ref>PMID:27576344</ref>

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

==See Also==
*[[Selenocysteine synthase|Selenocysteine synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: French RL]]
[[Category: Simonovic M]]