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| <StructureSection load='1ddk' size='340' side='right'caption='[[1ddk]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='1ddk' size='340' side='right'caption='[[1ddk]], [[Resolution|resolution]] 3.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1ddk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DDK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1DDK FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1ddk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DDK FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3.1Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dd6|1dd6]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ddk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ddk OCA], [https://pdbe.org/1ddk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ddk RCSB], [https://www.ebi.ac.uk/pdbsum/1ddk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ddk 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=1ddk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ddk OCA], [http://pdbe.org/1ddk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ddk RCSB], [http://www.ebi.ac.uk/pdbsum/1ddk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ddk ProSAT]</span></td></tr> | |
| </table> | | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/Q79MP6_PSEAI Q79MP6_PSEAI] |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </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=1ddk ConSurf]. | | </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=1ddk ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Metallo beta-lactamase enzymes confer antibiotic resistance to bacteria by catalyzing the hydrolysis of beta-lactam antibiotics. This relatively new form of resistance is spreading unchallenged as there is a current lack of potent and selective inhibitors of metallo beta-lactamases. Reported here are the crystal structures of the native IMP-1 metallo beta-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor, 2-[5-(1-tetrazolylmethyl)thien-3-yl]-N-[2-(mercaptomethyl)-4 -(phenylb utyrylglycine)]. The structures were determined by molecular replacement, and refined to 3.1 A (native) and 2.0 A (complex) resolution. Binding of the inhibitor in the active site induces a conformational change that results in closing of the flap and transforms the active site groove into a tunnel-shaped cavity enclosing 83% of the solvent accessible surface area of the inhibitor. The inhibitor binds in the active site through interactions with residues that are conserved among metallo beta-lactamases; the inhibitor's carboxylate group interacts with Lys161, and the main chain amide nitrogen of Asn167. In the "oxyanion hole", the amide carbonyl oxygen of the inhibitor interacts through a water molecule with the side chain of Asn167, the inhibitor's thiolate bridges the two Zn(II) ions in the active site displacing the bridging water, and the phenylbutyryl side chain binds in a hydrophobic pocket (S1) at the base of the flap. The flap is displaced 2.9 A compared to the unbound structure, allowing Trp28 to interact edge-to-face with the inhibitor's thiophene ring. The similarities between this inhibitor and the beta-lactam substrates suggest a mode of substrate binding and the role of the conserved residues in the active site. It appears that the metallo beta-lactamases bind their substrates by establishing a subset of binding interactions near the catalytic center with conserved characteristic chemical groups of the beta-lactam substrates. These interactions are complemented by additional nonspecific binding between the more variable groups in the substrates and the flexible flap. This unique mode of binding of the mercaptocarboxylate inhibitor in the enzyme active site provides a binding model for metallo beta-lactamase inhibition with utility for future drug design.
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| Crystal structure of the IMP-1 metallo beta-lactamase from Pseudomonas aeruginosa and its complex with a mercaptocarboxylate inhibitor: binding determinants of a potent, broad-spectrum inhibitor.,Concha NO, Janson CA, Rowling P, Pearson S, Cheever CA, Clarke BP, Lewis C, Galleni M, Frere JM, Payne DJ, Bateson JH, Abdel-Meguid SS Biochemistry. 2000 Apr 18;39(15):4288-98. PMID:10757977<ref>PMID:10757977</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1ddk" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Beta-lactamase]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Abdel-Meguid, S S]] | | [[Category: Pseudomonas aeruginosa]] |
| [[Category: Bateson, J H]] | | [[Category: Abdel-Meguid SS]] |
| [[Category: Cheever, C A]] | | [[Category: Bateson JH]] |
| [[Category: Clarke, B P]] | | [[Category: Cheever CA]] |
| [[Category: Concha, N O]] | | [[Category: Clarke BP]] |
| [[Category: Frere, J M]] | | [[Category: Concha NO]] |
| [[Category: Galleni, M]] | | [[Category: Frere JM]] |
| [[Category: Janson, C A]] | | [[Category: Galleni M]] |
| [[Category: Lewis, C]] | | [[Category: Janson CA]] |
| [[Category: Payne, D J]] | | [[Category: Lewis C]] |
| [[Category: Pearson, S]] | | [[Category: Payne DJ]] |
| [[Category: Rowling, P]] | | [[Category: Pearson S]] |
| [[Category: Binuclear metal center]]
| | [[Category: Rowling P]] |
| [[Category: Hydrolase]]
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| [[Category: Imp-1 metallo beta-lactamase]]
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| [[Category: Zn beta-lactamase]]
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