6c89: Difference between revisions
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==NDM-1 Beta-Lactamase Exhibits Differential Active Site Sequence Requirements for the Hydrolysis of Penicillin versus Carbapenem Antibiotics== | |||
<StructureSection load='6c89' size='340' side='right'caption='[[6c89]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6c89]] is a 4 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=6C89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C89 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]] 1.7500615Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6c89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c89 OCA], [https://pdbe.org/6c89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c89 RCSB], [https://www.ebi.ac.uk/pdbsum/6c89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c89 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/E5KIY2_ECOLX E5KIY2_ECOLX] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
New Delhi metallo-beta-lactamase-1 exhibits a broad substrate profile for hydrolysis of the penicillin, cephalosporin and 'last resort' carbapenems, and thus confers bacterial resistance to nearly all beta-lactam antibiotics. Here we address whether the high catalytic efficiency for hydrolysis of these diverse substrates is reflected by similar sequence and structural requirements for catalysis, i.e., whether the same catalytic machinery is used to achieve hydrolysis of each class. Deep sequencing of randomized single codon mutation libraries that were selected for resistance to representative antibiotics reveal stringent sequence requirements for carbapenem versus penicillin or cephalosporin hydrolysis. Further, the residue positions required for hydrolysis of penicillins and cephalosporins are a subset of those required for carbapenem hydrolysis. Thus, while a common core of residues is used for catalysis of all substrates, carbapenem hydrolysis requires an additional set of residues to achieve catalytic efficiency comparable to that for penicillins and cephalosporins. | |||
Differential active site requirements for NDM-1 beta-lactamase hydrolysis of carbapenem versus penicillin and cephalosporin antibiotics.,Sun Z, Hu L, Sankaran B, Prasad BVV, Palzkill T Nat Commun. 2018 Oct 30;9(1):4524. doi: 10.1038/s41467-018-06839-1. PMID:30375382<ref>PMID:30375382</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6c89" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Palzkill T]] | |||
[[Category: Sankaran B]] | |||
[[Category: Sun Z]] | |||
Latest revision as of 17:58, 4 October 2023
NDM-1 Beta-Lactamase Exhibits Differential Active Site Sequence Requirements for the Hydrolysis of Penicillin versus Carbapenem AntibioticsNDM-1 Beta-Lactamase Exhibits Differential Active Site Sequence Requirements for the Hydrolysis of Penicillin versus Carbapenem Antibiotics
Structural highlights
FunctionPublication Abstract from PubMedNew Delhi metallo-beta-lactamase-1 exhibits a broad substrate profile for hydrolysis of the penicillin, cephalosporin and 'last resort' carbapenems, and thus confers bacterial resistance to nearly all beta-lactam antibiotics. Here we address whether the high catalytic efficiency for hydrolysis of these diverse substrates is reflected by similar sequence and structural requirements for catalysis, i.e., whether the same catalytic machinery is used to achieve hydrolysis of each class. Deep sequencing of randomized single codon mutation libraries that were selected for resistance to representative antibiotics reveal stringent sequence requirements for carbapenem versus penicillin or cephalosporin hydrolysis. Further, the residue positions required for hydrolysis of penicillins and cephalosporins are a subset of those required for carbapenem hydrolysis. Thus, while a common core of residues is used for catalysis of all substrates, carbapenem hydrolysis requires an additional set of residues to achieve catalytic efficiency comparable to that for penicillins and cephalosporins. Differential active site requirements for NDM-1 beta-lactamase hydrolysis of carbapenem versus penicillin and cephalosporin antibiotics.,Sun Z, Hu L, Sankaran B, Prasad BVV, Palzkill T Nat Commun. 2018 Oct 30;9(1):4524. doi: 10.1038/s41467-018-06839-1. PMID:30375382[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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