3iwo

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{{Seed}}
 
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[[Image:3iwo.jpg|left|200px]]
 
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==X-ray crystal structure of the extended-spectrum AmpC Y221G mutant beta-lactamase at 1.90 Angstrom resolution==
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The line below this paragraph, containing "STRUCTURE_3iwo", creates the "Structure Box" on the page.
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<StructureSection load='3iwo' size='340' side='right'caption='[[3iwo]], [[Resolution|resolution]] 1.90&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'>[[3iwo]] 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=3IWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IWO 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]] 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=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene></td></tr>
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{{STRUCTURE_3iwo| PDB=3iwo | 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=3iwo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iwo OCA], [https://pdbe.org/3iwo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iwo RCSB], [https://www.ebi.ac.uk/pdbsum/3iwo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iwo 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/iw/3iwo_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=3iwo 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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Preorganization of enzyme active sites for substrate recognition typically comes at a cost to the stability of the folded form of the protein; consequently, enzymes can be dramatically stabilized by substitutions that attenuate the size and preorganization "strain" of the active site. How this stability-activity tradeoff constrains enzyme evolution has remained less certain, and it is unclear whether one should expect major stability insults as enzymes mutate towards new activities or how these new activities manifest structurally. These questions are both germane and easy to study in beta-lactamases, which are evolving on the timescale of years to confer resistance to an ever-broader spectrum of beta-lactam antibiotics. To explore whether stability is a substantial constraint on this antibiotic resistance evolution, we investigated extended-spectrum mutants of class C beta-lactamases, which had evolved new activity versus third-generation cephalosporins. Five mutant enzymes had between 100-fold and 200-fold increased activity against the antibiotic cefotaxime in enzyme assays, and the mutant enzymes all lost thermodynamic stability (from 1.7 kcal mol(-)(1) to 4.1 kcal mol(-)(1)), consistent with the stability-function hypothesis. Intriguingly, several of the substitutions were 10-20 A from the catalytic serine; the question of how they conferred extended-spectrum activity arose. Eight structures, including complexes with inhibitors and extended-spectrum antibiotics, were determined by X-ray crystallography. Distinct mechanisms of action, including changes in the flexibility and ground-state structures of the enzyme, are revealed for each mutant. These results explain the structural bases for the antibiotic resistance conferred by these substitutions and their corresponding decrease in protein stability, which will constrain the evolution of new antibiotic resistance.
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===X-ray crystal structure of the extended-spectrum AmpC Y221G mutant beta-lactamase at 1.90 Angstrom resolution===
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Structural bases for stability-function tradeoffs in antibiotic resistance.,Thomas VL, McReynolds AC, Shoichet BK J Mol Biol. 2010 Feb 12;396(1):47-59. Epub 2009 Nov 10. PMID:19913034<ref>PMID:19913034</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 3iwo" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19913034}}, 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 19913034 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19913034}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Escherichia coli K-12]]
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3IWO is a 2 chains structure with sequences 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=3IWO OCA].
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[[Category: Large Structures]]
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[[Category: Shoichet BK]]
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==Reference==
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[[Category: Thomas VL]]
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<ref group="xtra">PMID:19913034</ref><references group="xtra"/>
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[[Category: Beta-lactamase]]
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[[Category: Escherichia coli]]
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[[Category: Shoichet, B K.]]
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[[Category: Thomas, V L.]]
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[[Category: Antibiotic resistance]]
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[[Category: Beta-lactamase]]
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[[Category: Cephalosporinase]]
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[[Category: Extended-spectrum antibiotic resistance]]
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[[Category: Hydrolase]]
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[[Category: Periplasm]]
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[[Category: Serine hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 17 10:29:21 2010''
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Current revision

X-ray crystal structure of the extended-spectrum AmpC Y221G mutant beta-lactamase at 1.90 Angstrom resolution

PDB ID 3iwo

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OCA

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