2i72

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[[Image:2i72.jpg|left|200px]]
 
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{{Structure
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==AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid==
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|PDB= 2i72 |SIZE=350|CAPTION= <scene name='initialview01'>2i72</scene>, resolution 2.200&Aring;
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<StructureSection load='2i72' size='340' side='right'caption='[[2i72]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=VA1:{5-[(DIFORMYLAMINO)METHYL]-1-BENZOTHIEN-2-YL}BORONIC ACID'>VA1</scene>
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<table><tr><td colspan='2'>[[2i72]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I72 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]] 2.2&#8491;</td></tr>
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|GENE= ampC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VA1:{5-[(DIFORMYLAMINO)METHYL]-1-BENZOTHIEN-2-YL}BORONIC+ACID'>VA1</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=2i72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i72 OCA], [https://pdbe.org/2i72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i72 RCSB], [https://www.ebi.ac.uk/pdbsum/2i72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i72 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
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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/i7/2i72_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2i72 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Benzo[b]thiophene-2-ylboronic acid, 1, is a 27 nM inhibitor of the class C beta-lactamase AmpC and potentiates the activity of beta-lactam antibiotics in bacteria that express this and related enzymes. As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria, where the minimum inhibitor concentration of compound 1 is in the mid-micromolar range. Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X-ray crystallography, structure-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria.
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'''AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid'''
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Optimizing cell permeation of an antibiotic resistance inhibitor for improved efficacy.,Venturelli A, Tondi D, Cancian L, Morandi F, Cannazza G, Segatore B, Prati F, Amicosante G, Shoichet BK, Costi MP J Med Chem. 2007 Nov 15;50(23):5644-54. Epub 2007 Oct 23. PMID:17956081<ref>PMID:17956081</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2i72" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Benzo[b]thiophene-2-ylboronic acid, 1, is a 27 nM inhibitor of the class C beta-lactamase AmpC and potentiates the activity of beta-lactam antibiotics in bacteria that express this and related enzymes. As is often true, the potency of compound 1 against the enzymes is much attenuated in cell culture against Gram negative bacteria, where the minimum inhibitor concentration of compound 1 is in the mid-micromolar range. Here, we modulated the properties of this lead to enhance its ability to cross the membrane, using a combination of X-ray crystallography, structure-based design, and application of physical models of outer membrane crossing. This strategy led us to derivatives with substantially improved permeability. Also, the greater solubility of these compounds allowed us to measure their efficacy at higher concentrations than with the lead 1, leading to higher maximum potentiation of the antibiotic effect of ceftazidime on resistant bacteria.
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2I72 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I72 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Optimizing cell permeation of an antibiotic resistance inhibitor for improved efficacy., Venturelli A, Tondi D, Cancian L, Morandi F, Cannazza G, Segatore B, Prati F, Amicosante G, Shoichet BK, Costi MP, J Med Chem. 2007 Nov 15;50(23):5644-54. Epub 2007 Oct 23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17956081 17956081]
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[[Category: Beta-lactamase]]
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[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Amicosante, G.]]
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[[Category: Amicosante G]]
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[[Category: Cancian, L.]]
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[[Category: Cancian L]]
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[[Category: Cannazza, G.]]
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[[Category: Cannazza G]]
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[[Category: Costi, M P.]]
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[[Category: Costi MP]]
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[[Category: Morandi, F.]]
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[[Category: Morandi F]]
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[[Category: Prati, F.]]
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[[Category: Prati F]]
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[[Category: Segatore, B.]]
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[[Category: Segatore B]]
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[[Category: Shoichet, B K.]]
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[[Category: Shoichet BK]]
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[[Category: Tondi, D.]]
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[[Category: Tondi D]]
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[[Category: Venturelli, A.]]
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[[Category: Venturelli A]]
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[[Category: VA1]]
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[[Category: ampc]]
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[[Category: beta-lactamase]]
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[[Category: cephalosporinase]]
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[[Category: serine hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:26:14 2008''
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Current revision

AmpC beta-lactamase in complex with 5-diformylaminomethyl-benzo[b]thiophen-2-boronic acid

PDB ID 2i72

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