6rd3: Difference between revisions
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==Crystal structure of the wild type OmpK36 from Klebsiella pneumonia== | |||
<StructureSection load='6rd3' size='340' side='right'caption='[[6rd3]], [[Resolution|resolution]] 1.98Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6rd3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RD3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RD3 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]] 1.98Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6rd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rd3 OCA], [https://pdbe.org/6rd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rd3 RCSB], [https://www.ebi.ac.uk/pdbsum/6rd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rd3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/D6QLY0_KLEPN D6QLY0_KLEPN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Carbapenem-resistance in Klebsiella pneumoniae (KP) sequence type ST258 is mediated by carbapenemases (e.g. KPC-2) and loss or modification of the major non-selective porins OmpK35 and OmpK36. However, the mechanism underpinning OmpK36-mediated resistance and consequences of these changes on pathogenicity remain unknown. By solving the crystal structure of a clinical ST258 OmpK36 variant we provide direct structural evidence of pore constriction, mediated by a di-amino acid (Gly115-Asp116) insertion into loop 3, restricting diffusion of both nutrients (e.g. lactose) and Carbapenems. In the presence of KPC-2 this results in a 16-fold increase in MIC to Meropenem. Additionally, the Gly-Asp insertion impairs bacterial growth in lactose-containing medium and confers a significant in vivo fitness cost in a murine model of ventilator-associated pneumonia. Our data suggests that the continuous selective pressure imposed by widespread Carbapenem utilisation in hospital settings drives the expansion of KP expressing Gly-Asp insertion mutants, despite an associated fitness cost. | |||
OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo.,Wong JLC, Romano M, Kerry LE, Kwong HS, Low WW, Brett SJ, Clements A, Beis K, Frankel G Nat Commun. 2019 Sep 2;10(1):3957. doi: 10.1038/s41467-019-11756-y. PMID:31477712<ref>PMID:31477712</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6rd3" style="background-color:#fffaf0;"></div> | ||
[[Category: Beis | |||
[[Category: Romano | ==See Also== | ||
*[[Porin 3D structures|Porin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | |||
[[Category: Beis K]] | |||
[[Category: Kwong J]] | |||
[[Category: Romano M]] | |||
Latest revision as of 15:19, 24 January 2024
Crystal structure of the wild type OmpK36 from Klebsiella pneumoniaCrystal structure of the wild type OmpK36 from Klebsiella pneumonia
Structural highlights
FunctionPublication Abstract from PubMedCarbapenem-resistance in Klebsiella pneumoniae (KP) sequence type ST258 is mediated by carbapenemases (e.g. KPC-2) and loss or modification of the major non-selective porins OmpK35 and OmpK36. However, the mechanism underpinning OmpK36-mediated resistance and consequences of these changes on pathogenicity remain unknown. By solving the crystal structure of a clinical ST258 OmpK36 variant we provide direct structural evidence of pore constriction, mediated by a di-amino acid (Gly115-Asp116) insertion into loop 3, restricting diffusion of both nutrients (e.g. lactose) and Carbapenems. In the presence of KPC-2 this results in a 16-fold increase in MIC to Meropenem. Additionally, the Gly-Asp insertion impairs bacterial growth in lactose-containing medium and confers a significant in vivo fitness cost in a murine model of ventilator-associated pneumonia. Our data suggests that the continuous selective pressure imposed by widespread Carbapenem utilisation in hospital settings drives the expansion of KP expressing Gly-Asp insertion mutants, despite an associated fitness cost. OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo.,Wong JLC, Romano M, Kerry LE, Kwong HS, Low WW, Brett SJ, Clements A, Beis K, Frankel G Nat Commun. 2019 Sep 2;10(1):3957. doi: 10.1038/s41467-019-11756-y. PMID:31477712[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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