3hlw: Difference between revisions
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< | ==CTX-M-9 S70G in complex with cefotaxime== | ||
<StructureSection load='3hlw' size='340' side='right'caption='[[3hlw]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3hlw]] 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=3HLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HLW FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CE3:(6R,7R)-3-(ACETYLOXYMETHYL)-7-[[(2Z)-2-(2-AMINO-1,3-THIAZOL-4-YL)-2-METHOXYIMINO-ETHANOYL]AMINO]-8-OXO-5-THIA-1-AZABICYCLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC+ACID'>CE3</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3hlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlw OCA], [https://pdbe.org/3hlw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlw RCSB], [https://www.ebi.ac.uk/pdbsum/3hlw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hl/3hlw_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=3hlw ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-Lactamase-mediated resistance to beta-lactam antibiotics poses a major threat to our antibiotic armamentarium. Among beta-lactamases, a significant threat comes from enzymes that hydrolyze extended-spectrum cephalosporins such as cefotaxime. Among the enzymes that exhibit this phenotype, the CTX-M family is found worldwide. These enzymes have a small active site, which makes it difficult to explain how they hydrolyze the bulky extended-spectrum cephalosporins into the binding site. We investigated noncovalent substrate recognition and product release in CTX-M enzymes using steered molecular dynamics simulation and X-ray diffraction. An arginine residue located far from the binding site favors the capture and tracking of substrates during entrance into the catalytic pocket. We show that the accommodation of extended-spectrum cephalosporins by CTX-M enzymes induced subtle changes in the active site and established a high density of electrostatic interactions. Interestingly, the product of the catalytic reaction initiates its own release because of steric hindrances and electrostatic repulsions. This suggests that there exists a general mechanism for product release for all members of the beta-lactamase family and probably for most carboxypeptidases. | |||
Structural insights into substrate recognition and product expulsion in CTX-M enzymes.,Delmas J, Leyssene D, Dubois D, Birck C, Vazeille E, Robin F, Bonnet R J Mol Biol. 2010 Jul 2;400(1):108-20. Epub 2010 May 7. PMID:20452359<ref>PMID:20452359</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3hlw" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Bonnet | [[Category: Large Structures]] | ||
[[Category: Delmas | [[Category: Bonnet R]] | ||
[[Category: Dubois | [[Category: Delmas J]] | ||
[[Category: Leyssne | [[Category: Dubois D]] | ||
[[Category: Robin | [[Category: Leyssne D]] | ||
[[Category: Vazeille | [[Category: Robin F]] | ||
[[Category: Vazeille E]] | |||
Latest revision as of 18:50, 1 November 2023
CTX-M-9 S70G in complex with cefotaximeCTX-M-9 S70G in complex with cefotaxime
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedbeta-Lactamase-mediated resistance to beta-lactam antibiotics poses a major threat to our antibiotic armamentarium. Among beta-lactamases, a significant threat comes from enzymes that hydrolyze extended-spectrum cephalosporins such as cefotaxime. Among the enzymes that exhibit this phenotype, the CTX-M family is found worldwide. These enzymes have a small active site, which makes it difficult to explain how they hydrolyze the bulky extended-spectrum cephalosporins into the binding site. We investigated noncovalent substrate recognition and product release in CTX-M enzymes using steered molecular dynamics simulation and X-ray diffraction. An arginine residue located far from the binding site favors the capture and tracking of substrates during entrance into the catalytic pocket. We show that the accommodation of extended-spectrum cephalosporins by CTX-M enzymes induced subtle changes in the active site and established a high density of electrostatic interactions. Interestingly, the product of the catalytic reaction initiates its own release because of steric hindrances and electrostatic repulsions. This suggests that there exists a general mechanism for product release for all members of the beta-lactamase family and probably for most carboxypeptidases. Structural insights into substrate recognition and product expulsion in CTX-M enzymes.,Delmas J, Leyssene D, Dubois D, Birck C, Vazeille E, Robin F, Bonnet R J Mol Biol. 2010 Jul 2;400(1):108-20. Epub 2010 May 7. PMID:20452359[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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