View source for 9n51


==Crosslinked Crystal Structure of Human Mitochondrial Ketosynthase, OXSM, and Crosslinker-crypto Human Mitochondrial Acyl Carrier Protein, C8Cl-mACP==
<StructureSection load='9n51' size='340' side='right'caption='[[9n51]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9n51]] is a 6 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=9N51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9N51 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]] 2.31&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BMZ:[(3~{R})-2,2-dimethyl-4-[[3-[2-(octanoylamino)ethylamino]-3-oxidanylidene-propyl]amino]-3-oxidanyl-4-oxidanylidene-butyl]+dihydrogen+phosphate'>A1BMZ</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=9n51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9n51 OCA], [https://pdbe.org/9n51 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9n51 RCSB], [https://www.ebi.ac.uk/pdbsum/9n51 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9n51 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OXSM_HUMAN OXSM_HUMAN] May play a role in the biosynthesis of lipoic acid as well as longer chain fatty acids required for optimal mitochondrial function.<ref>PMID:15668256</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Although ketosynthases in bacterial type II fatty acid biosynthesis have been extensively studied, the human mitochondrial ketosynthase, OXSM, remains incompletely characterized. Contrary to the assumption that the role of mitochondrial fatty acid biosynthesis is limited to the production of the lipoic acid precursor octanoate, recent studies suggest an ability to produce longer chain fatty acids. Here, we employ covalent, dual site-selective cross-linkers to trap the interactions between OXSM and its mitochondrial acyl carrier protein partner, mACP. Two high-resolution crystal structures that capture OXSM bound to mACP provide molecular details of the conformational changes that guide the chain elongation process. We identify key protein * protein and protein * substrate interactions that regulate the transacylation and condensation steps associated with this process. We also observe a conserved gating mechanism previously identified in bacterial type II ketosynthases. Complemented by site-directed mutagenesis and activity analyses, these findings provide detailed insight into the selectivity of the OXSM substrate. This study explores how the OXSM can elongate fatty acids larger than eight carbons, mirroring that of its bacterial type II progenitor.

Role of Human Mitochondrial Ketosynthase in Long-Chain Fatty Acid Biosynthesis.,Suo Y, Jiang Z, Heberlig GW, Wang EY, Sankaran B, La Clair JJ, Burkart MD J Am Chem Soc. 2025 Sep 10;147(36):33248-33255. doi: 10.1021/jacs.5c10318. Epub , 2025 Sep 2. PMID:40891531<ref>PMID:40891531</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9n51" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Burkart MD]]
[[Category: Chen A]]
[[Category: Heberlig GW]]
[[Category: Jiang Z]]
[[Category: La Clair JJ]]
[[Category: Sankaran B]]
[[Category: Suo Y]]
[[Category: Wang EY]]