View source for 4chl


==Human Ethylmalonic Encephalopathy Protein 1 (hETHE1)==
<StructureSection load='4chl' size='340' side='right'caption='[[4chl]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4chl]] 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=4CHL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CHL 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]] 2.61&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</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=4chl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4chl OCA], [https://pdbe.org/4chl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4chl RCSB], [https://www.ebi.ac.uk/pdbsum/4chl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4chl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ETHE1_HUMAN ETHE1_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Ethylmalonic Encephalopathy Protein 1 (ETHE1) catalyzes the oxygen dependent oxidation of glutathione persulfide to give persulfite and glutathione. Mutations to the hETHE1 gene compromise sulfide metabolism leading to the genetic disease ethylmalonic encephalopathy. hETHE1 is a mono-iron binding member of the metallo-beta-lactamase fold superfamily. We report crystallographic analysis of hETHE1 in complex with iron to 2.6 A resolution. hETHE1 contains an alphabetabetaalpha MBL-fold, which supports metal-binding by the side-chains of an aspartate- and two histidine- residues; three water molecules complete an octahedral coordination of iron. The iron binding hETHE1 enzyme is related to the 'classical' di-zinc binding MBL hydrolases involved in antibiotic resistance, but has distinctive features. The two histidine-, and aspartate- residues involved in iron-binding in ETHE1, occupy similar positions to those observed by both the zinc 1 and zinc 2 binding sites in classical MBLs. The active site of hETHE1 is very similar to an ETHE1-like enzyme from Arabidopsis thaliana (60% sequence identity). A channel leading to the active site is sufficiently large to accommodate a glutathione persulfide substrate. Some of the observed hETHE1 clinical mutations cluster in the active site region. The structure will serve as a basis for detailed functional and mechanistic studies on ETHE1, and will be useful in the development of selective MBL inhibitors.

Crystal Structure of Human Persulfide Dioxygenase: Structural Basis of Ethylmalonic Encephalopathy.,Pettinati I, Brem J, McDonough MA, Schofield CJ Hum Mol Genet. 2015 Jan 16. pii: ddv007. PMID:25596185<ref>PMID:25596185</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4chl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brem J]]
[[Category: McDonough MA]]
[[Category: Pettinati I]]
[[Category: Schofield CJ]]