6pqc: Difference between revisions
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<StructureSection load='6pqc' size='340' side='right'caption='[[6pqc]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='6pqc' size='340' side='right'caption='[[6pqc]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6pqc]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6pqc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PQC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PQC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CEF:CEFOTAXIME,+C3+CLEAVED,+OPEN,+BOUND+FORM'>CEF</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CEF:CEFOTAXIME,+C3+CLEAVED,+OPEN,+BOUND+FORM'>CEF</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6pqc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pqc OCA], [https://pdbe.org/6pqc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pqc RCSB], [https://www.ebi.ac.uk/pdbsum/6pqc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pqc ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A160YKM3_CLODI A0A160YKM3_CLODI] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6pqc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6pqc" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Clostridioides difficile]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Smith | [[Category: Smith CA]] | ||
[[Category: Vakulenko | [[Category: Vakulenko SB]] | ||
Latest revision as of 10:33, 11 October 2023
Structure of cefotaxime-CDD-1 beta-lactamase complexStructure of cefotaxime-CDD-1 beta-lactamase complex
Structural highlights
FunctionPublication Abstract from PubMedClass D beta-lactamases, enzymes that degrade beta-lactam antibiotics and are widely spread in Gram-negative bacteria, were for a long time not known in Gram-positive organisms. Recently, these enzymes were identified in various non-pathogenic Bacillus species and subsequently in Clostridioides difficile, a major clinical pathogen associated with high morbidity and mortality rates. Comparison of the BPU-1 enzyme from Bacillus pumilus with the CDD-1 and CDD-2 enzymes from C. difficile demonstrated that the latter enzymes have broadened their substrate profile to efficiently hydrolyze the expanded-spectrum methoxyimino cephalosporins, cefotaxime and ceftriaxone. These two antibiotics are major contributors to the development of C. difficile infection, as they suppress sensitive bacterial microflora in the gut but fail to kill the pathogen which is highly resistant to these drugs. To gain insight into the structural features that contribute to the expansion of the substrate profile of CDD enzymes compared to BPU-1, we solved the crystal structures of CDD-1 and its complex with cefotaxime. Comparison of CDD-1 structures with those of class D enzymes from Gram-negative bacteria showed that in the cefotaxime-CDD-1 complex, the antibiotic is bound in a substantially different mode due to structural differences in the enzymes' active sites. We also found that CDD-1 has a uniquely long Omega-loop when compared to all other class D beta-lactamases. This Omega-loop extension allows it to engage in hydrogen bonding with the acylated cefotaxime, thus providing additional stabilizing interactions with the substrate which could be responsible for the high catalytic activity of the enzyme for expanded-spectrum cephalosporins. The crystal structures of CDD-1, the intrinsic class D beta-lactamase from the pathogenic Gram-positive bacterium Clostridioides difficile, and its complex with cefotaxime.,Stewart NK, Smith CA, Toth M, Stasyuk A, Vakulenko SB J Struct Biol. 2019 Sep 21. pii: S1047-8477(19)30202-3. doi:, 10.1016/j.jsb.2019.09.008. PMID:31550535[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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