4gd8: Difference between revisions
New page: '''Unreleased structure''' The entry 4gd8 is ON HOLD Authors: Pattanaik, P., van den Akker, F. Description: SHV-1 beta-lactamase in complex with penam sulfone SA3-53 |
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==SHV-1 beta-lactamase in complex with penam sulfone SA3-53== | |||
<StructureSection load='4gd8' size='340' side='right'caption='[[4gd8]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4gd8]] is a 1 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=4GD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GD8 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]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=MXF:(2S,3R)-4-(2-AMINOETHYLCARBAMOYLOXY)-2-[(2-METHANOYLINDOLIZIN-3-YL)AMINO]-3-METHYL-3-SULFINO-BUTANOIC+ACID'>MXF</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=4gd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gd8 OCA], [https://pdbe.org/4gd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gd8 RCSB], [https://www.ebi.ac.uk/pdbsum/4gd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gd8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLA1_KLEPN BLA1_KLEPN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bacterial beta-lactamase enzymes are in large part responsible for the decreased ability of beta-lactam antibiotics to combat infections. The inability to overcome beta-lactamase mediated resistance spurred the development of inhibitors with penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, "suicide-type" inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of beta-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-based inhibitors of these common class A serine beta-lactamases. | |||
Structures of SHV-1 beta-lactamase with penem and penam sulfone inhibitors that form cyclic intermediates stabilized by carbonyl conjugation.,Ke W, Pattanaik P, Bethel CR, Sheri A, Buynak JD, Bonomo RA, van den Akker F PLoS One. 2012;7(11):e49035. doi: 10.1371/journal.pone.0049035. Epub 2012 Nov 8. PMID:23145056<ref>PMID:23145056</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4gd8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | |||
[[Category: Pattanaik P]] | |||
[[Category: Van den Akker F]] | |||
Latest revision as of 05:56, 21 November 2024
SHV-1 beta-lactamase in complex with penam sulfone SA3-53SHV-1 beta-lactamase in complex with penam sulfone SA3-53
Structural highlights
FunctionPublication Abstract from PubMedBacterial beta-lactamase enzymes are in large part responsible for the decreased ability of beta-lactam antibiotics to combat infections. The inability to overcome beta-lactamase mediated resistance spurred the development of inhibitors with penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, "suicide-type" inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of beta-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-based inhibitors of these common class A serine beta-lactamases. Structures of SHV-1 beta-lactamase with penem and penam sulfone inhibitors that form cyclic intermediates stabilized by carbonyl conjugation.,Ke W, Pattanaik P, Bethel CR, Sheri A, Buynak JD, Bonomo RA, van den Akker F PLoS One. 2012;7(11):e49035. doi: 10.1371/journal.pone.0049035. Epub 2012 Nov 8. PMID:23145056[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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