4s2p
From Proteopedia
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==Crystal structure of unbound OXA-48== | ==Crystal structure of unbound OXA-48== | ||
| - | <StructureSection load='4s2p' size='340' side='right' caption='[[4s2p]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4s2p' size='340' side='right'caption='[[4s2p]], [[Resolution|resolution]] 1.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4s2p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S2P OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4s2p]] is a 2 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=4S2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S2P FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=4s2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s2p OCA], [https://pdbe.org/4s2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s2p RCSB], [https://www.ebi.ac.uk/pdbsum/4s2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s2p 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/BLO48_KLEPN BLO48_KLEPN] Class D beta-lactamase which confers resistance to the beta-lactam antibiotics, including amoxicillin, and moderate resistance to cephalosporins and carbapenems such as cephalothin and imipenem; in the DH10B strain of E.coli (PubMed:14693513). Acts via hydrolysis of the beta-lactam ring (PubMed:14693513, PubMed:19477418, PubMed:27073009, PubMed:38161376). Has oxacillin-, cephalothin- and imipenem-hydrolyzing activities (PubMed:14693513, PubMed:19477418, PubMed:27073009, PubMed:38161376).<ref>PMID:14693513</ref> <ref>PMID:19477418</ref> <ref>PMID:27073009</ref> <ref>PMID:38161376</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Emerging beta-lactamase-mediated resistance is threatening the clinical utility of the single most prominent class of antibacterial agents used in medicine, the beta-lactams. The diazabicyclooctane avibactam is able to inhibit a wider range of serine beta-lactamases than has been previously observed with beta-lactamase inhibitors such as the widely prescribed clavulanic acid. However, despite its broad-spectrum activity, variable levels of inhibition have been observed for molecular class D beta-lactamases. In order to better understand the molecular basis and spectrum of inhibition by avibactam, we provide structural and mechanistic analysis of the compound in complex with important class A and D serine beta-lactamases. Herein, we reveal the 1.7- and 2.0-A-resolution crystal structures of avibactam covalently bound to class D beta-lactamases OXA-10 and OXA-48. Furthermore, a kinetic analysis of key active-site mutants for class A beta-lactamase CTX-M-15 allows us to propose a validated mechanism for avibactam-mediated beta-lactamase inhibition including a unique role for S130, which acts as a general base. This study provides molecular insights that will aid in the design and development of avibactam-based chemotherapeutic agents effective against emerging drug-resistant microorganisms. | ||
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| + | Molecular Mechanism of Avibactam-Mediated beta-Lactamase Inhibition.,King DT, King AM, Lal SM, Wright GD, Strynadka NC ACS Infect Dis. 2015 Apr 10;1(4):175-84. doi: 10.1021/acsinfecdis.5b00007. Epub, 2015 Feb 11. PMID:27622530<ref>PMID:27622530</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4s2p" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Klebsiella pneumoniae]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: King DT]] |
| - | [[Category: | + | [[Category: Strynadka NCJ]] |
Current revision
Crystal structure of unbound OXA-48
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