1kr3

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{{Seed}}
 
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[[Image:1kr3.png|left|200px]]
 
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==Crystal Structure of the Metallo beta-Lactamase from Bacteroides fragilis (CfiA) in Complex with the Tricyclic Inhibitor SB-236050.==
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The line below this paragraph, containing "STRUCTURE_1kr3", creates the "Structure Box" on the page.
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<StructureSection load='1kr3' size='340' side='right'caption='[[1kr3]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1kr3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KR3 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.5&#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=113:7,8-DIHYDROXY-1-METHOXY-3-METHYL-10-OXO-4,10-DIHYDRO-1H,3H-PYRANO[4,3-B]CHROMENE-9-CARBOXYLIC+ACID'>113</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1kr3| PDB=1kr3 | SCENE= }}
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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=1kr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kr3 OCA], [https://pdbe.org/1kr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kr3 RCSB], [https://www.ebi.ac.uk/pdbsum/1kr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kr3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BLAB_BACFG BLAB_BACFG] Can hydrolyze carbapenem compounds.
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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/kr/1kr3_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=1kr3 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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This work describes the discovery and characterization of a novel series of tricyclic natural product-derived metallo-beta-lactamase inhibitors. Natural product screening of the Bacillus cereus II enzyme identified an extract from a strain of Chaetomium funicola with inhibitory activity against metallo-beta-lactamases. SB236050, SB238569, and SB236049 were successfully extracted and purified from this extract. The most active of these compounds was SB238569, which possessed K(i) values of 79, 17, and 3.4 microM for the Bacillus cereus II, Pseudomonas aeruginosa IMP-1, and Bacteroides fragilis CfiA metallo-beta-lactamases, respectively, yet none of the compounds exhibited any inhibitory activity against the Stenotrophomonas maltophilia L-1 metallo-beta-lactamase (50% inhibitory concentration &gt; 1,000 microM). The lack of activity against angiotensin-converting enzyme and serine beta-lactamases demonstrated the selective nature of these compounds. The crystal structure of SB236050 complexed in the active site of CfiA has been obtained to a resolution of 2.5 A. SB236050 exhibits key polar interactions with Lys184, Asn193, and His162 and a stacking interaction with the indole ring of Trp49 in the flap, which is in the closed conformation over the active site groove. SB236050 and SB238569 also demonstrate good antibacterial synergy with meropenem. Eight micrograms of SB236050 per ml gave rise to an eightfold drop in the MIC of meropenem for two clinical isolates of B. fragilis producing CfiA, making these strains sensitive to meropenem (MIC &lt; or = 4 microg/ml). Consequently, this series of metallo-beta-lactamase inhibitors exhibit the most promising antibacterial synergy activity so far observed against organisms producing metallo-beta-lactamases.
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===Crystal Structure of the Metallo beta-Lactamase from Bacteroides fragilis (CfiA) in Complex with the Tricyclic Inhibitor SB-236050.===
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Identification of a series of tricyclic natural products as potent broad-spectrum inhibitors of metallo-beta-lactamases.,Payne DJ, Hueso-Rodriguez JA, Boyd H, Concha NO, Janson CA, Gilpin M, Bateson JH, Cheever C, Niconovich NL, Pearson S, Rittenhouse S, Tew D, Diez E, Perez P, De La Fuente J, Rees M, Rivera-Sagredo A Antimicrob Agents Chemother. 2002 Jun;46(6):1880-6. PMID:12019104<ref>PMID:12019104</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 1kr3" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_12019104}}, adds the Publication Abstract to the page
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*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 12019104 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_12019104}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1KR3 is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KR3 OCA].
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==Reference==
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<ref group="xtra">PMID:12019104</ref><references group="xtra"/>
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[[Category: Bacteroides fragilis]]
[[Category: Bacteroides fragilis]]
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[[Category: Beta-lactamase]]
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[[Category: Large Structures]]
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[[Category: Bateson, J H.]]
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[[Category: Bateson JH]]
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[[Category: Boyd, H.]]
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[[Category: Boyd H]]
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[[Category: Cheever, C.]]
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[[Category: Cheever C]]
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[[Category: Concha, N O.]]
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[[Category: Concha NO]]
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[[Category: Dez, E.]]
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[[Category: Dez E]]
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[[Category: Fuente, J de la.]]
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[[Category: Gilpin M]]
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[[Category: Gilpin, M.]]
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[[Category: Hueso-Rodrguez JA]]
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[[Category: Hueso-Rodrguez, J A.]]
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[[Category: Janson CA]]
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[[Category: Janson, C A.]]
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[[Category: Niconovich NL]]
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[[Category: Niconovich, N L.]]
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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: Prez P]]
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[[Category: Prez, P.]]
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[[Category: Rees M]]
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[[Category: Rees, M.]]
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[[Category: Rittenhouse S]]
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[[Category: Rittenhouse, S.]]
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[[Category: Rivera-Sagredo A]]
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[[Category: Rivera-Sagredo, A.]]
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[[Category: Tew D]]
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[[Category: Tew, D.]]
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[[Category: De la Fuente J]]
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[[Category: Beta sandwich]]
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[[Category: Beta-lactamase]]
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[[Category: Metallo]]
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[[Category: Protein-inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 15:53:11 2009''
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Current revision

Crystal Structure of the Metallo beta-Lactamase from Bacteroides fragilis (CfiA) in Complex with the Tricyclic Inhibitor SB-236050.

PDB ID 1kr3

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