5l6j - Revision history

OCA at 07:48, 7 February 2024

OCA — Wed, 07 Feb 2024 07:48:06 GMT

←Older revision		Revision as of 07:48, 7 February 2024
Line 4:		Line 4:
	== 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]] 2.68Å</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®/PubMed®, 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/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:07, 2 March 2023

OCA — Thu, 02 Mar 2023 06:07:48 GMT

←Older revision		Revision as of 06:07, 2 March 2023
Line 3:		Line 3:
	<StructureSection load='5l6j' size='340' side='right'caption='[[5l6j]], [[Resolution\|resolution]] 2.68Å' scene=''>		<StructureSection load='5l6j' size='340' side='right'caption='[[5l6j]], [[Resolution\|resolution]] 2.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5l6j]] is a 4 chain structure. 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 [~~http~~://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='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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/E1_ubiquitin-activating_enzyme E1 ubiquitin-activating enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.45 6.2.1.45] </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>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l6j OCA], [~~http~~://pdbe.org/5l6j PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5l6j RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5l6j PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5l6j ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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. [[http://www.uniprot.org/uniprot/RS27A_YEAST RS27A_YEAST]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). 40S ribosomal protein S31 is a component of the 40S subunit of the ribosome (By similarity).	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:

	==See Also==		==See Also==
-	*[[Ubiquitin activating enzyme\|Ubiquitin activating enzyme]]	+	*[[3D structures of Ubiquitin activating enzyme\|3D structures of Ubiquitin activating enzyme]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: E1 ubiquitin-activating enzyme]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Misra, M~~]]	+	[[Category: Saccharomyces cerevisiae S288C]]
-	[[Category: ~~Schindelin, H~~]]	+	[[Category: Misra M]]
-	[[Category: ~~Adenosyl sulfamate]]~~	+	[[Category: Schindelin H]]
-	~~[[Category: E1 enzyme]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Uba1 inhibitor]]~~	+
-	~~[[Category: Ubiquitin activation~~]]	+

OCA at 06:57, 5 August 2020

OCA — Wed, 05 Aug 2020 06:57:53 GMT

←Older revision		Revision as of 06:57, 5 August 2020
Line 1:		Line 1:

	==Uba1 in complex with Ub-MLN7243 covalent adduct==		==Uba1 in complex with Ub-MLN7243 covalent adduct==
-	<StructureSection load='5l6j' size='340' side='right' caption='[[5l6j]], [[Resolution\|resolution]] 2.68Å' scene=''>	+	<StructureSection load='5l6j' size='340' side='right'caption='[[5l6j]], [[Resolution\|resolution]] 2.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5l6j]] is a 4 chain structure. 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 [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5L6J FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5l6j]] is a 4 chain structure. 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 [http://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"><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='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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/E1_ubiquitin-activating_enzyme E1 ubiquitin-activating enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.45 6.2.1.45] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/E1_ubiquitin-activating_enzyme E1 ubiquitin-activating enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.45 6.2.1.45] </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=5l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l6j OCA], [http://pdbe.org/5l6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l6j RCSB], [http://www.ebi.ac.uk/pdbsum/5l6j PDBsum], [http://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'>[http://proteopedia.org/fgij/fg.htm?mol=5l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l6j OCA], [http://pdbe.org/5l6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l6j RCSB], [http://www.ebi.ac.uk/pdbsum/5l6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l6j ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5l6j" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5l6j" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ubiquitin activating enzyme\|Ubiquitin activating enzyme]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: E1 ubiquitin-activating enzyme]]		[[Category: E1 ubiquitin-activating enzyme]]
		+	[[Category: Large Structures]]
	[[Category: Misra, M]]		[[Category: Misra, M]]
	[[Category: Schindelin, H]]		[[Category: Schindelin, H]]

OCA at 03:48, 6 September 2017

OCA — Wed, 06 Sep 2017 03:48:54 GMT

←Older revision		Revision as of 03:48, 6 September 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5l6j is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Uba1 in complex with Ub-MLN7243 covalent adduct==
		+	<StructureSection load='5l6j' size='340' side='right' caption='[[5l6j]], [[Resolution\|resolution]] 2.68Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5l6j]] is a 4 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L6J FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/E1_ubiquitin-activating_enzyme E1 ubiquitin-activating enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.45 6.2.1.45] </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=5l6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l6j OCA], [http://pdbe.org/5l6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l6j RCSB], [http://www.ebi.ac.uk/pdbsum/5l6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l6j ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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. [[http://www.uniprot.org/uniprot/RS27A_YEAST RS27A_YEAST]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). 40S ribosomal protein S31 is a component of the 40S subunit of the ribosome (By similarity).
		+	<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.

-	~~Authors~~:	+	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>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5l6j" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: E1 ubiquitin-activating enzyme]]
		+	[[Category: Misra, M]]
		+	[[Category: Schindelin, H]]
		+	[[Category: Adenosyl sulfamate]]
		+	[[Category: E1 enzyme]]
		+	[[Category: Ligase]]
		+	[[Category: Uba1 inhibitor]]
		+	[[Category: Ubiquitin activation]]

OCA at 14:38, 9 September 2016

OCA — Fri, 09 Sep 2016 14:38:23 GMT

←Older revision		Revision as of 14:38, 9 September 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5l6j is ON HOLD	+	The entry 5l6j is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 00:45, 13 July 2016

OCA — Wed, 13 Jul 2016 00:45:25 GMT

←Older revision		Revision as of 00:45, 13 July 2016
Line 3:		Line 3:
	The entry 5l6j is ON HOLD		The entry 5l6j is ON HOLD

-	Authors: ~~Misra, M., Schindelin, H.~~	+	Authors:

-	Description: ~~Uba1 in complex with Ub-MLN7243 covalent adduct~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Schindelin, H]]
-	[[Category: Misra, M]]

OCA: Protected "5l6j" [edit=sysop:move=sysop]

OCA — Mon, 20 Jun 2016 13:56:38 GMT

Protected "5l6j" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:56, 20 June 2016

OCA: New page: '''Unreleased structure''' The entry 5l6j is ON HOLD Authors: Misra, M., Schindelin, H. Description: Uba1 in complex with Ub-MLN7243 covalent adduct Category: Unreleased Structures...

OCA — Mon, 20 Jun 2016 13:56:37 GMT

New page: '''Unreleased structure''' The entry 5l6j is ON HOLD Authors: Misra, M., Schindelin, H. Description: Uba1 in complex with Ub-MLN7243 covalent adduct Category: Unreleased Structures...

New page

'''Unreleased structure'''

The entry 5l6j is ON HOLD

Authors: Misra, M., Schindelin, H.

Description: Uba1 in complex with Ub-MLN7243 covalent adduct
[[Category: Unreleased Structures]]
[[Category: Schindelin, H]]
[[Category: Misra, M]]