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4gah
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gah]] 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=4GAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GAH FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gah]] 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=4GAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GAH FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ET:[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-4-OXIDANYL-3-PHOSPHONOOXY-OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+[(3R)-2,2-DIMETHYL-3-OXIDANYL-4-OXIDANYLIDENE-4-[[3-OXIDANYLIDENE-3-[2-[(2R)-2-OXIDANYLUNDECYL]SULFANYLETHYLAMINO]PROPYL]AMINO]BUTYL]+HYDROGEN+PHOSPHATE'>0ET</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0ET:[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-4-OXIDANYL-3-PHOSPHONOOXY-OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+[(3R)-2,2-DIMETHYL-3-OXIDANYL-4-OXIDANYLIDENE-4-[[3-OXIDANYLIDENE-3-[2-[(2R)-2-OXIDANYLUNDECYL]SULFANYLETHYLAMINO]PROPYL]AMINO]BUTYL]+HYDROGEN+PHOSPHATE'>0ET</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=4gah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gah OCA], [https://pdbe.org/4gah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gah RCSB], [https://www.ebi.ac.uk/pdbsum/4gah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gah ProSAT]</span></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=4gah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gah OCA], [https://pdbe.org/4gah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gah RCSB], [https://www.ebi.ac.uk/pdbsum/4gah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gah ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | [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 == | ||
| - | Human THEM4 (hTHEM4) is comprised of a catalytically active hotdog-fold acyl-CoA thioesterase domain and an N-terminal domain of unknown fold and function. hTHEM4 has been linked to Akt1 regulation and cell apoptosis. Herein, we report the X-ray structure of hHTEM4 bound with undecan-2-one-CoA. Structure guided mutagenesis was carried out to confirm the catalytic residues. The N-terminal domain is shown to be partially comprised of irregular and flexible secondary structure, reminiscent of a protein-binding domain. We demonstrate direct hTHEM4-Akt1 binding by immunoprecipitation and by inhibition of Akt1 kinase activity, thus providing independent evidence that hTHEM4 is an Akt1 negative regulator. | ||
| - | |||
| - | Correlation of Structure and Function in the Human Hotdog-fold Enzyme hTHEM4.,Zhao H, Lim K, Choudry A, Latham JA, Pathak MC, Dominguez D, Luo L, Herzberg O, Dunaway-Mariano D Biochemistry. 2012 Aug 21;51(33):6490-2. Epub 2012 Aug 9. PMID:22871024<ref>PMID:22871024</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gah" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Human acyl-CoA thioesterases 4 in complex with undecan-2-one-CoA inhibitor
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