View source for 4ypa


==ASH1L SET domain Q2265A mutant in complex with S-adenosyl methionine (SAM)==
<StructureSection load='4ypa' size='340' side='right'caption='[[4ypa]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ypa]] 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=4YPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YPA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4ypa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypa OCA], [https://pdbe.org/4ypa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ypa RCSB], [https://www.ebi.ac.uk/pdbsum/4ypa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypa ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ASH1L_HUMAN ASH1L_HUMAN] Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me).<ref>PMID:21239497</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ASH1L (absent, small, or homeotic-like 1) is a histone methyltransferase (HMTase) involved in gene activation that is overexpressed in multiple forms of cancer. Previous studies of ASH1L's catalytic SET domain identified an autoinhibitory loop that blocks access of histone substrate to the enzyme active site. Here, we used both nuclear magnetic resonance and X-ray crystallography to identify conformational dynamics in the ASH1L autoinhibitory loop. Using site-directed mutagenesis, we found that point mutations in the autoinhibitory loop that perturb the structure of the SET domain result in decreased enzyme activity, indicating that the autoinhibitory loop is not a simple gate to the active site but is rather a key feature critical to ASH1L function. We also identified a second loop in the SET-I subdomain of ASH1L that experiences conformational dynamics, and we trapped two different conformations of this loop using crystallographic studies. Mutation of the SET-I loop led to a large decrease in ASH1L enzymatic activity in addition to a significant conformational change in the SET-I loop, demonstrating the importance of the structure and dynamics of the SET-I loop to ASH1L function. Furthermore, we found that three C-terminal chromatin-interacting domains greatly enhance ASH1L enzymatic activity and that ASH1L requires native nucleosome substrate for robust activity. Our study illuminates the role of concerted conformational dynamics in ASH1L function and identifies structural features important for ASH1L enzymatic activity.

Two Loops Undergoing Concerted Dynamics Regulate the Activity of the ASH1L Histone Methyltransferase.,Rogawski DS, Ndoj J, Cho HJ, Maillard I, Grembecka J, Cierpicki T Biochemistry. 2015 Aug 25. PMID:26292256<ref>PMID:26292256</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ypa" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cho HJ]]
[[Category: Cierpicki T]]
[[Category: Grembecka J]]
[[Category: Maillard I]]
[[Category: Ndoj J]]
[[Category: Rogawski DS]]