4ynp: Difference between revisions
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==ASH1L SET domain S2259M mutant in complex with S-adenosyl methionine (SAM)== | ==ASH1L SET domain S2259M mutant in complex with S-adenosyl methionine (SAM)== | ||
<StructureSection load='4ynp' size='340' side='right' caption='[[4ynp]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='4ynp' size='340' side='right' caption='[[4ynp]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ynp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YNP FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ynp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YNP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YNP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ynm|4ynm]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ynm|4ynm]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ASH1L, KIAA1420, KMT2H ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ynp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ynp OCA], [http://pdbe.org/4ynp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ynp RCSB], [http://www.ebi.ac.uk/pdbsum/4ynp PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ynp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ynp OCA], [http://pdbe.org/4ynp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ynp RCSB], [http://www.ebi.ac.uk/pdbsum/4ynp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ynp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Histone-lysine N-methyltransferase]] | [[Category: Histone-lysine N-methyltransferase]] | ||
[[Category: Human]] | |||
[[Category: Cho, H J]] | [[Category: Cho, H J]] | ||
[[Category: Cierpicki, T]] | [[Category: Cierpicki, T]] | ||
Revision as of 15:19, 6 November 2017
ASH1L SET domain S2259M mutant in complex with S-adenosyl methionine (SAM)ASH1L SET domain S2259M mutant in complex with S-adenosyl methionine (SAM)
Structural highlights
Function[ASH1L_HUMAN] Histone methyltransferase specifically methylating 'Lys-36' of histone H3 (H3K36me).[1] Publication Abstract from PubMedASH1L (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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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