5l6j: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5l6j]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L6J FirstGlance]. <br>
<table><tr><td colspan='2'>[[5l6j]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L6J FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=61T:[(1~{R},2~{R},3~{S},4~{R})-2,3-bis(oxidanyl)-4-[[2-[3-(trifluoromethylsulfanyl)phenyl]pyrazolo[1,5-a]pyrimidin-7-yl]amino]cyclopentyl]methyl+sulfamate'>61T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.68&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=61T:[(1~{R},2~{R},3~{S},4~{R})-2,3-bis(oxidanyl)-4-[[2-[3-(trifluoromethylsulfanyl)phenyl]pyrazolo[1,5-a]pyrimidin-7-yl]amino]cyclopentyl]methyl+sulfamate'>61T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l6j OCA], [https://pdbe.org/5l6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l6j RCSB], [https://www.ebi.ac.uk/pdbsum/5l6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l6j 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=5l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l6j OCA], [https://pdbe.org/5l6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l6j RCSB], [https://www.ebi.ac.uk/pdbsum/5l6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l6j ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/UBA1_YEAST UBA1_YEAST] Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin-E1 thioester and free AMP.
[https://www.uniprot.org/uniprot/UBA1_YEAST UBA1_YEAST] Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin-E1 thioester and free AMP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Targeting the activating enzymes (E1) of ubiquitin (Ub) and ubiquitin-like modifiers (Ubls) has emerged as a promising anti-cancer strategy, possibly overcoming the ineffectiveness of proteasome inhibitors against solid tumors. Here, we report crystal structures of the yeast ubiquitin E1 (Uba1) with three adenosyl sulfamate inhibitors exhibiting different E1 specificities, which are all covalently linked to ubiquitin. The structures illustrate how the chemically diverse inhibitors are accommodated within the adenylation active site. When compared with the previously reported structures of various E1 enzymes, our structures provide the basis of the preferences of these inhibitors for different Ub/Ubl-activating enzymes. In vitro inhibition assays and molecular dynamics simulations validated the specificities of the inhibitors as deduced from the structures. Taken together, the structures establish a framework for the development of additional compounds targeting E1 enzymes, which will display higher potency and selectivity.
Dissecting the Specificity of Adenosyl Sulfamate Inhibitors Targeting the Ubiquitin-Activating Enzyme.,Misra M, Kuhn M, Lobel M, An H, Statsyuk AV, Sotriffer C, Schindelin H Structure. 2017 Jul 5;25(7):1120-1129.e3. doi: 10.1016/j.str.2017.05.001. Epub, 2017 Jun 1. PMID:28578874<ref>PMID:28578874</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5l6j" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
== References ==
<references/>
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</StructureSection>
</StructureSection>
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