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1fsw

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(New page: 200px<br /><applet load="1fsw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fsw, resolution 1.90&Aring;" /> '''AMPC BETA-LACTAMASE ...)
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[[Image:1fsw.gif|left|200px]]<br /><applet load="1fsw" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1fsw, resolution 1.90&Aring;" />
 
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'''AMPC BETA-LACTAMASE FROM E. COLI COMPLEXED WITH INHIBITOR CEPHALOTHINBORONIC ACID'''<br />
 
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==Overview==
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==AMPC BETA-LACTAMASE FROM E. COLI COMPLEXED WITH INHIBITOR CEPHALOTHINBORONIC ACID==
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BACKGROUND: Penicillins and cephalosporins are among the most widely used, and successful antibiotics. The emergence of resistance to these, beta-lactams, most often through bacterial expression of beta-lactamases, threatens public health. To understand how beta-lactamases recognize their, substrates, it would be helpful to know their binding energies., Unfortunately, these have been difficult to measure because beta-lactams, form covalent adducts with beta-lactamases. This has complicated, functional analyses and inhibitor design. RESULTS: To investigate the, contribution to interaction energy of the key amide (R1) side chain of, beta-lactam antibiotics, eight acylglycineboronic acids that bear the side, chains of characteristic penicillins and cephalosporins, as well as four, other analogs, were synthesized. These transition-state analogs form, reversible adducts with serine beta-lactamases. Therefore, binding, energies can be calculated directly from K(i) values. The K(i) values, measured span four orders of magnitude against the Group I beta-lactamase, AmpC and three orders of magnitude against the Group II beta-lactamase, TEM-1. The acylglycineboronic acids have K(i) values as low as 20 nM, against AmpC and as low as 390 nM against TEM-1. The inhibitors showed, little activity against serine proteases, such as chymotrypsin. R1 side, chains characteristic of beta-lactam inhibitors did not have better, affinity for AmpC than did side chains characteristic of beta-lactam, substrates. Two of the inhibitors reversed the resistance of pathogenic, bacteria to beta-lactams in cell culture. Structures of two inhibitors in, their complexes with AmpC were determined by X-ray crystallography to 1.90, A and 1.75 A resolution; these structures suggest interactions that are, important to the affinity of the inhibitors. CONCLUSIONS:, Acylglycineboronic acids allow us to begin to dissect interaction energies, between beta-lactam side chains and beta-lactamases. Surprisingly, there, is little correlation between the affinity contributed by R1 side chains, and their occurrence in beta-lactam inhibitors or beta-lactam substrates, of serine beta-lactamases. Nevertheless, presented in acylglycineboronic, acids, these side chains can lead to inhibitors with high affinities and, specificities. The structures of their complexes with AmpC give a, molecular context to their affinities and may guide the design of, anti-resistance compounds in this series.
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<StructureSection load='1fsw' size='340' side='right'caption='[[1fsw]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1fsw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FSW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FSW FirstGlance]. <br>
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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]] 1.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTB:N-2-THIOPHEN-2-YL-ACETAMIDE+BORONIC+ACID'>CTB</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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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=1fsw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fsw OCA], [https://pdbe.org/1fsw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fsw RCSB], [https://www.ebi.ac.uk/pdbsum/1fsw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fsw 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/fs/1fsw_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=1fsw ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1FSW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with PO4 and CTB as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FSW OCA].
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Energetic, structural, and antimicrobial analyses of beta-lactam side chain recognition by beta-lactamases., Caselli E, Powers RA, Blasczcak LC, Wu CY, Prati F, Shoichet BK, Chem Biol. 2001 Jan;8(1):17-31. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11182316 11182316]
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[[Category: Escherichia coli K-12]]
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[[Category: Beta-lactamase]]
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[[Category: Large Structures]]
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[[Category: Escherichia coli]]
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[[Category: Blaszczak LC]]
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[[Category: Single protein]]
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[[Category: Caselli E]]
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[[Category: Blaszczak, L.C.]]
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[[Category: Powers RA]]
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[[Category: Caselli, E.]]
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[[Category: Prati F]]
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[[Category: Powers, R.A.]]
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[[Category: Shoichet BK]]
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[[Category: Prati, F.]]
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[[Category: Wu CY]]
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[[Category: Shoichet, B.K.]]
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[[Category: Wu, C.Y.]]
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[[Category: CTB]]
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[[Category: PO4]]
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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://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 15:14:50 2007''
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AMPC BETA-LACTAMASE FROM E. COLI COMPLEXED WITH INHIBITOR CEPHALOTHINBORONIC ACID

PDB ID 1fsw

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