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| | <StructureSection load='6i9y' size='340' side='right'caption='[[6i9y]], [[Resolution|resolution]] 2.14Å' scene=''> | | <StructureSection load='6i9y' size='340' side='right'caption='[[6i9y]], [[Resolution|resolution]] 2.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6i9y]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Sporosarcina_pasteurii Sporosarcina pasteurii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I9Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6i9y]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Sporosarcina_pasteurii Sporosarcina pasteurii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9Y FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</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]] 2.14Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=CXM:N-CARBOXYMETHIONINE'>CXM</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</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/Urease Urease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.5 3.5.1.5] </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=6i9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9y OCA], [https://pdbe.org/6i9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9y RCSB], [https://www.ebi.ac.uk/pdbsum/6i9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9y 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=6i9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9y OCA], [http://pdbe.org/6i9y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i9y RCSB], [http://www.ebi.ac.uk/pdbsum/6i9y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9y ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/URE1_SPOPA URE1_SPOPA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6i9y" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6i9y" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Urease 3D structures|Urease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Sporosarcina pasteurii]] | | [[Category: Sporosarcina pasteurii]] |
| - | [[Category: Urease]]
| + | [[Category: Cianci M]] |
| - | [[Category: Cianci, M]] | + | [[Category: Ciurli S]] |
| - | [[Category: Ciurli, S]] | + | [[Category: Mazzei L]] |
| - | [[Category: Mazzei, L]] | + | |
| - | [[Category: Gold compound]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metal-based ndrug]]
| + | |
| - | [[Category: Nickel]]
| + | |
| Structural highlights
6i9y is a 3 chain structure with sequence from Sporosarcina pasteurii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.14Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
URE1_SPOPA
Publication Abstract from PubMed
The nickel-dependent enzyme urease is a virulence factor for a large number of critical human pathogens, making this enzyme a potential target of therapeutics for the treatment of resistant bacterial infections. In the search for novel urease inhibitors, five selected coordination and organometallic Au(III) compounds containing N(wedge)N or C(wedge)N and C(wedge)N(wedge)N ligands were tested for their inhibitory effects against Canavalia ensiformis (jack bean) urease. The results showed potent inhibition effects with IC50 values in the nanomolar range. The 2.14 A resolution crystal structure of Sporosarcina pasteurii urease inhibited by the most effective Au(III) compound [Au(PbImMe)Cl2]PF6 (PbImMe = 1-methyl-2-(pyridin-2-yl)-benzimidazole) reveals the presence of two Au ions bound to the conserved triad alphaCys322/alphaHis323/alphaMet367. The binding of the Au ions to these residues blocks the movement of a flap, located at the edge of the active site channel and essential for enzyme catalysis, completely obliterating the catalytic activity of urease. Overall, the obtained results constitute the basis for the design of new gold complexes as selective urease inhibitors with future antibacterial applications.
Inhibition Mechanism of Urease by Au(III) Compounds Unveiled by X-ray Diffraction Analysis.,Mazzei L, Wenzel MN, Cianci M, Palombo M, Casini A, Ciurli S ACS Med Chem Lett. 2019 Jan 4;10(4):564-570. doi: 10.1021/acsmedchemlett.8b00585., eCollection 2019 Apr 11. PMID:30996797[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mazzei L, Wenzel MN, Cianci M, Palombo M, Casini A, Ciurli S. Inhibition Mechanism of Urease by Au(III) Compounds Unveiled by X-ray Diffraction Analysis. ACS Med Chem Lett. 2019 Jan 4;10(4):564-570. doi: 10.1021/acsmedchemlett.8b00585., eCollection 2019 Apr 11. PMID:30996797 doi:http://dx.doi.org/10.1021/acsmedchemlett.8b00585
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