|
|
| (11 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:2yz3.jpg|left|200px]] | |
| | | | |
| - | {{Structure
| + | ==Crystallographic Investigation of Inhibition Mode of the VIM-2 Metallo-beta-lactamase from Pseudomonas aeruginosa with Mercaptocarboxylate Inhibitor== |
| - | |PDB= 2yz3 |SIZE=350|CAPTION= <scene name='initialview01'>2yz3</scene>, resolution 2.30Å
| + | <StructureSection load='2yz3' size='340' side='right'caption='[[2yz3]], [[Resolution|resolution]] 2.30Å' scene=''> |
| - | |SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Residue+A+301'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Residue+A+302'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Residue+B+303'>AC3</scene>, <scene name='pdbsite=AC4:Zn+Binding+Site+For+Residue+B+304'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Residue+B+501'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Residue+A+502'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Residue+A+503'>AC7</scene>, <scene name='pdbsite=AC8:So4+Binding+Site+For+Residue+B+504'>AC8</scene>, <scene name='pdbsite=AC9:M5p+Binding+Site+For+Residue+A+401'>AC9</scene> and <scene name='pdbsite=BC1:M5p+Binding+Site+For+Residue+B+402'>BC1</scene>
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=M5P:(S)-2-(MERCAPTOMETHYL)-5-PHENYLPENTANOIC+ACID'>M5P</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
| + | <table><tr><td colspan='2'>[[2yz3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YZ3 FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | |GENE= VIM-2, bla VIM-2, blaVIM-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=303 Pseudomonas putida])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M5P:(S)-2-(MERCAPTOMETHYL)-5-PHENYLPENTANOIC+ACID'>M5P</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2yz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yz3 OCA], [https://pdbe.org/2yz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2yz3 RCSB], [https://www.ebi.ac.uk/pdbsum/2yz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2yz3 ProSAT]</span></td></tr> |
| - | |RELATEDENTRY= | + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2yz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yz3 OCA], [http://www.ebi.ac.uk/pdbsum/2yz3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2yz3 RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/Q7BJM5_PSEPU Q7BJM5_PSEPU] |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yz/2yz3_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2yz3 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Crystallographic Investigation of Inhibition Mode of the VIM-2 Metallo-beta-lactamase from Pseudomonas aeruginosa with Mercaptocarboxylate Inhibitor'''
| + | ==See Also== |
| - | | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | The VIM-2 metallo-beta-lactamase enzyme from Pseudomonas aeruginosa catalyzes the hydrolysis of most beta-lactam antibiotics including carbapenems, and there are currently no potent inhibitors of such enzymes. We found rac-2-omega-phenylpropyl-3-mercaptopropionic acid, phenylC3SH, to be a potent inhibitor of VIM-2. The structure of the VIM-2-phenylC3SH complex was determined by X-ray crystallography to 2.3 A. The structure revealed that the thiol group of phenylC3SH bridged to the two zinc(II) ions and the phenyl group interacted with Tyr67(47) on loop1 near the active site, by pi-pi stacking interactions. The methylene group interacted with Phe61(42) located at the bottom of loop1 through CH-pi interactions. Dynamic movements were observed in Arg228(185) and Asn233(190) on loop2, compared with the native structure (PDB code: 1KO3 ). These results suggest that the above-mentioned four residues play important roles in the binding and recognition of inhibitors or substrates and in stabilizing a loop in the VIM-2 enzyme.
| + | [[Category: Large Structures]] |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 2YZ3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YZ3 OCA].
| + | |
| - | | + | |
| - | ==Reference==
| + | |
| - | Crystallographic investigation of the inhibition mode of a VIM-2 metallo-beta-lactamase from Pseudomonas aeruginosa by a mercaptocarboxylate inhibitor., Yamaguchi Y, Jin W, Matsunaga K, Ikemizu S, Yamagata Y, Wachino J, Shibata N, Arakawa Y, Kurosaki H, J Med Chem. 2007 Dec 27;50(26):6647-53. Epub 2007 Dec 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18052313 18052313]
| + | |
| - | [[Category: Beta-lactamase]] | + | |
| | [[Category: Pseudomonas putida]] | | [[Category: Pseudomonas putida]] |
| - | [[Category: Single protein]]
| + | [[Category: Arakawa Y]] |
| - | [[Category: Arakawa, Y.]] | + | [[Category: Kurosaki H]] |
| - | [[Category: Kurosaki, H.]] | + | [[Category: Yamagata Y]] |
| - | [[Category: Yamagata, Y.]] | + | [[Category: Yamaguchi Y]] |
| - | [[Category: Yamaguchi, Y.]] | + | |
| - | [[Category: enzyme-inhibitor complex]]
| + | |
| - | [[Category: hydrolase]]
| + | |
| - | [[Category: metallo-beta-lactamase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:16:43 2008''
| + | |
