|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5um6' size='340' side='right'caption='[[5um6]], [[Resolution|resolution]] 2.79Å' scene=''> | | <StructureSection load='5um6' size='340' side='right'caption='[[5um6]], [[Resolution|resolution]] 2.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5um6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Fission_yeast Fission yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UM6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UM6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5um6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UM6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UM6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8E7:2-(decylamino)ethane-1-thiol'>8E7</scene>, <scene name='pdbligand=8EA:N-(2-{[(4-chlorophenyl)methyl]disulfanyl}ethyl)decan-1-amine'>8EA</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]] 2.794Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ptr3, SPBC1604.21c, SPBC211.09 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284812 Fission yeast])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8E7:2-(decylamino)ethane-1-thiol'>8E7</scene>, <scene name='pdbligand=8EA:N-(2-{[(4-chlorophenyl)methyl]disulfanyl}ethyl)decan-1-amine'>8EA</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=5um6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5um6 OCA], [https://pdbe.org/5um6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5um6 RCSB], [https://www.ebi.ac.uk/pdbsum/5um6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5um6 ProSAT]</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=5um6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5um6 OCA], [http://pdbe.org/5um6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5um6 RCSB], [http://www.ebi.ac.uk/pdbsum/5um6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5um6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBA1_SCHPO UBA1_SCHPO]] 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_SCHPO UBA1_SCHPO] 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 22: |
Line 21: |
| | | | |
| | ==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: Fission yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aldana-Masangkay, G]] | + | [[Category: Schizosaccharomyces pombe 972h-]] |
| - | [[Category: Atkison, J H]] | + | [[Category: Aldana-Masangkay G]] |
| - | [[Category: Chen, Y]] | + | [[Category: Atkison JH]] |
| - | [[Category: Lv, Z]] | + | [[Category: Chen Y]] |
| - | [[Category: Olsen, S K]] | + | [[Category: Lv Z]] |
| - | [[Category: Yuan, L]] | + | [[Category: Olsen SK]] |
| - | [[Category: Atp binding]]
| + | [[Category: Yuan L]] |
| - | [[Category: Atp/mg binding]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Ligase activity]]
| + | |
| - | [[Category: Ligase-ligase inhibitor complex]]
| + | |
| - | [[Category: Rossmann-like fold]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Ubiquitin activating enzyme]]
| + | |
| - | [[Category: Ubiquitin e2 binding]]
| + | |
| - | [[Category: Ubiquitin-like fold]]
| + | |
| Structural highlights
Function
UBA1_SCHPO 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.
Publication Abstract from PubMed
E1 enzymes for ubiquitin (Ub) and Ub-like modifiers (Ubls) harbor two catalytic activities that are required for Ub/Ubl activation: adenylation and thioester bond formation. Structural studies of the E1 for the Ubl small ubiquitin-like modifier (SUMO) revealed a single active site that is transformed by a conformational switch that toggles its competency for catalysis of these two distinct chemical reactions. Although the mechanisms of adenylation and thioester bond formation revealed by SUMO E1 structures are thought to be conserved in Ub E1, there is currently a lack of structural data supporting this hypothesis. Here, we present a structure of Schizosaccharomyces pombe Uba1 in which the second catalytic cysteine half-domain (SCCH domain) harboring the catalytic cysteine has undergone a 106 degrees rotation that results in a completely different network of intramolecular interactions between the SCCH and adenylation domains and translocation of the catalytic cysteine 12 A closer to the Ub C terminus compared with previous Uba1 structures. SCCH domain alternation is accompanied by conformational changes within the Uba1 adenylation domains that effectively disassemble the adenylation active site. Importantly, the structural and biochemical data suggest that domain alternation and remodeling of the adenylation active site are interconnected and are intrinsic structural features of Uba1 and that the overall structural basis for adenylation and thioester bond formation exhibited by SUMO E1 is indeed conserved in Ub E1. Finally, the mechanistic insights provided by the novel conformational snapshot of Uba1 presented in this study may guide efforts to develop small molecule inhibitors of this critically important enzyme that is an active target for anticancer therapeutics.
Domain alternation and active site remodeling are conserved structural features of ubiquitin E1.,Lv Z, Yuan L, Atkison JH, Aldana-Masangkay G, Chen Y, Olsen SK J Biol Chem. 2017 Jul 21;292(29):12089-12099. doi: 10.1074/jbc.M117.787622. Epub , 2017 Jun 1. PMID:28572513[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lv Z, Yuan L, Atkison JH, Aldana-Masangkay G, Chen Y, Olsen SK. Domain alternation and active site remodeling are conserved structural features of ubiquitin E1. J Biol Chem. 2017 Jul 21;292(29):12089-12099. doi: 10.1074/jbc.M117.787622. Epub , 2017 Jun 1. PMID:28572513 doi:http://dx.doi.org/10.1074/jbc.M117.787622
|
