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1dd6

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[[Image:1dd6.jpg|left|200px]]
 
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{{Structure
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==IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR==
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|PDB= 1dd6 |SIZE=350|CAPTION= <scene name='initialview01'>1dd6</scene>, resolution 2.00&Aring;
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<StructureSection load='1dd6' size='340' side='right'caption='[[1dd6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=MCI:(2-MERCAPTOMETHYL-4-PHENYL-BUTYRYLIMINO)-(5-TETRAZOL-1-YLMETHYL-THIOPHEN-2-YL)-ACETIC ACID'>MCI</scene>
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<table><tr><td colspan='2'>[[1dd6]] is a 2 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=1DD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DD6 FirstGlance]. <br>
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|ACTIVITY= [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]
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</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&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MCI:(2-MERCAPTOMETHYL-4-PHENYL-BUTYRYLIMINO)-(5-TETRAZOL-1-YLMETHYL-THIOPHEN-2-YL)-ACETIC+ACID'>MCI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1dd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dd6 OCA], [https://pdbe.org/1dd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dd6 RCSB], [https://www.ebi.ac.uk/pdbsum/1dd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dd6 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BLAB_SERMA BLAB_SERMA] Confers resistance to imipenem and broad-spectrum beta-lactams. Also hydrolyzes carbapenems.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dd/1dd6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1dd6 ConSurf].
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<div style="clear:both"></div>
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'''IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR'''
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==See Also==
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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[[Category: Large Structures]]
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==About this Structure==
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1DD6 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DD6 OCA].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/10757977 10757977]
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[[Category: Beta-lactamase]]
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[[Category: Pseudomonas aeruginosa]]
[[Category: Pseudomonas aeruginosa]]
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[[Category: Single protein]]
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[[Category: Abdel-Meguid SS]]
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[[Category: Abdel-Meguid, S S.]]
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[[Category: Bateson JH]]
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[[Category: Bateson, J H.]]
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[[Category: Cheever CA]]
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[[Category: Cheever, C A.]]
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[[Category: Clarke BP]]
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[[Category: Clarke, B P.]]
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[[Category: Concha NO]]
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[[Category: Concha, N O.]]
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[[Category: Frere JM]]
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[[Category: Frere, J M.]]
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[[Category: Galleni M]]
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[[Category: Galleni, M.]]
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[[Category: Janson CA]]
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[[Category: Janson, C A.]]
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[[Category: Lewis C]]
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[[Category: Lewis, C.]]
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[[Category: Payne DJ]]
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[[Category: Payne, D J.]]
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[[Category: Pearson S]]
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[[Category: Pearson, S.]]
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[[Category: Rowling P]]
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[[Category: Rowling, P.]]
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[[Category: MCI]]
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[[Category: SO4]]
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[[Category: ZN]]
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[[Category: imp-1 metallo beta-lactamase]]
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[[Category: mercaptocarboxylate inhibitor]]
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[[Category: metallo beta-lactamase inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:36:38 2008''
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Current revision

IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A MERCAPTOCARBOXYLATE INHIBITOR

PDB ID 1dd6

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