View source for 4ae8


==Crystal structure of human THEM4==
<StructureSection load='4ae8' size='340' side='right'caption='[[4ae8]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ae8]] is a 4 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=4AE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AE8 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]] 1.594&#8491;</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=4ae8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ae8 OCA], [https://pdbe.org/4ae8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ae8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ae8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ae8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/THEM4_HUMAN THEM4_HUMAN] Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays an role in mitochondrial fatty acid metabolism. Plays a role in the apoptotic process, possibly via its regulation of AKT1 activity. According to PubMed:11598301, inhibits AKT1 phosphorylation and activity. According to PubMed:17615157, enhances AKT1 activity by favoring its phosphorylation and translocation to plasma membrane.<ref>PMID:11598301</ref> <ref>PMID:17615157</ref> <ref>PMID:19453107</ref> <ref>PMID:19168129</ref> <ref>PMID:19421406</ref> <ref>PMID:22871024</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Acyl coenzyme A (acyl-CoA) thioesterases hydrolyze thioester bonds in acyl-CoA metabolites. The majority of mammalian thioesterases are alpha/beta-hydrolases and have been studied extensively. A second class of Hotdog-fold enzymes has been less well described. Here, we present a structural and functional analysis of a new mammalian mitochondrial thioesterase, Them5. Them5 and its paralog, Them4, adopt the classical Hotdog-fold structure and form homodimers in crystals. In vitro, Them5 shows strong thioesterase activity with long-chain acyl-CoAs. Loss of Them5 specifically alters the remodeling process of the mitochondrial phospholipid cardiolipin. Them5(-/-) mice show deregulation of lipid metabolism and the development of fatty liver, exacerbated by a high-fat diet. Consequently, mitochondrial morphology is affected, and functions such as respiration and beta-oxidation are impaired. The novel mitochondrial acyl-CoA thioesterase Them5 has a critical and specific role in the cardiolipin remodeling process, connecting it to the development of fatty liver and related conditions.

Acyl coenzyme a thioesterase them5/acot15 is involved in cardiolipin remodeling and Fatty liver development.,Zhuravleva E, Gut H, Hynx D, Marcellin D, Bleck CK, Genoud C, Cron P, Keusch JJ, Dummler B, Esposti MD, Hemmings BA Mol Cell Biol. 2012 Jul;32(14):2685-97. Epub 2012 May 14. PMID:22586271<ref>PMID:22586271</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ae8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bleck CKE]]
[[Category: Cron P]]
[[Category: Degli Esposti M]]
[[Category: Dummler B]]
[[Category: Genoud C]]
[[Category: Gut H]]
[[Category: Hemmings BA]]
[[Category: Hynx D]]
[[Category: Keusch JJ]]
[[Category: Marcellin D]]
[[Category: Zhuravleva E]]