View source for 8fzb


==Crystal structure of human FAM86A==
<StructureSection load='8fzb' size='340' side='right'caption='[[8fzb]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fzb]] is a 3 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=8FZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FZB 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]] 3.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=8fzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fzb OCA], [https://pdbe.org/8fzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fzb RCSB], [https://www.ebi.ac.uk/pdbsum/8fzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fzb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EF2KT_HUMAN EF2KT_HUMAN] Catalyzes the trimethylation of eukaryotic elongation factor 2 (EEF2) on 'Lys-525'.<ref>PMID:25231979</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
FAM86A is a class I lysine methyltransferase (KMT) that generates trimethylation on the eukaryotic translation elongation factor 2 (EEF2) at Lys525. Publicly available data from The Cancer Dependency Map project indicate high dependence of hundreds of human cancer cell lines on FAM86A expression. This classifies FAM86A among numerous other KMTs as potential targets for future anticancer therapies. However, selective inhibition of KMTs by small molecules can be challenging due to high conservation within the S-adenosyl methionine (SAM) cofactor binding domain among KMT subfamilies. Therefore, understanding the unique interactions within each KMT-substrate pair can facilitate developing highly specific inhibitors. The FAM86A gene encodes an N-terminal FAM86 domain of unknown function in addition to its C-terminal methyltransferase domain. Here, we used a combination of X-ray crystallography, the AlphaFold algorithms, and experimental biochemistry to identify an essential role of the FAM86 domain in mediating EEF2 methylation by FAM86A. To facilitate our studies, we also generated a selective EEF2K525 methyl antibody. Overall, this is the first report of a biological function for the FAM86 structural domain in any species and an example of a noncatalytic domain participating in protein lysine methylation. The interaction between the FAM86 domain and EEF2 provides a new strategy for developing a specific FAM86A small molecule inhibitor, and our results provide an example in which modeling a protein-protein interaction with AlphaFold expedites experimental biology.

The FAM86 domain of FAM86A confers substrate specificity to promote EEF2-Lys525 methylation.,Francis JW, Shao Z, Narkhede P, Trinh AT, Lu J, Song J, Gozani O J Biol Chem. 2023 Jul;299(7):104842. doi: 10.1016/j.jbc.2023.104842. Epub 2023 , May 18. PMID:37209825<ref>PMID:37209825</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fzb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lu J]]
[[Category: Shao Z]]
[[Category: Song J]]