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==X-ray crystallographic structure of CTX-M-9 S70G in complex with hydrolyzed benzylpenicillin== | |||
<StructureSection load='3hvf' size='340' side='right' caption='[[3hvf]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3hvf]] is a 2 chain structure with 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=3HVF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HVF FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PNK:(2R,4S)-2-{(R)-CARBOXY[(PHENYLACETYL)AMINO]METHYL}-5,5-DIMETHYL-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>PNK</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hlw|3hlw]], [[3hre|3hre]], [[3huo|3huo]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaCTX-M-9, blaCTX-M-9a, blaCTX-M-9b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hvf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hvf RCSB], [http://www.ebi.ac.uk/pdbsum/3hvf PDBsum]</span></td></tr> | |||
</table> | |||
== 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/hv/3hvf_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/chain_selection.php?pdb_ID=2ata 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> | |||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase|Beta-lactamase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Bonnet, R | [[Category: Bonnet, R]] | ||
[[Category: Delmas, J | [[Category: Delmas, J]] | ||
[[Category: Dubois, D | [[Category: Dubois, D]] | ||
[[Category: Leyssene, D | [[Category: Leyssene, D]] | ||
[[Category: Robin, F | [[Category: Robin, F]] | ||
[[Category: Vazeille, E | [[Category: Vazeille, E]] | ||
[[Category: B-lactam]] | [[Category: B-lactam]] | ||
[[Category: Benzylpenicillin]] | [[Category: Benzylpenicillin]] | ||
[[Category: Blse]] | [[Category: Blse]] | ||
[[Category: Ctx-m-9]] | [[Category: Ctx-m-9]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Penicillin]] | [[Category: Penicillin]] | ||
Revision as of 20:25, 18 December 2014
X-ray crystallographic structure of CTX-M-9 S70G in complex with hydrolyzed benzylpenicillinX-ray crystallographic structure of CTX-M-9 S70G in complex with hydrolyzed benzylpenicillin
Structural highlights
Evolutionary 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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