7q0y
From Proteopedia
(Difference between revisions)
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==Crystal structure of CTX-M-14 in complex with Bortezomib== | ==Crystal structure of CTX-M-14 in complex with Bortezomib== | ||
| - | <StructureSection load='7q0y' size='340' side='right'caption='[[7q0y]]' scene=''> | + | <StructureSection load='7q0y' size='340' side='right'caption='[[7q0y]], [[Resolution|resolution]] 1.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q0Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q0Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7q0y]] 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=7Q0Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q0Y FirstGlance]. <br> |
| - | </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=7q0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q0y OCA], [https://pdbe.org/7q0y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q0y RCSB], [https://www.ebi.ac.uk/pdbsum/7q0y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q0y ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BO2:N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE'>BO2</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7q0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q0y OCA], [https://pdbe.org/7q0y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q0y RCSB], [https://www.ebi.ac.uk/pdbsum/7q0y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q0y ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A0H3H219_KLEPH A0A0H3H219_KLEPH] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | beta-lactamases are a major cause of rapidly emerging and spreading antibiotic resistance. Currently beta-lactamase inhibitors (BLIs) in clinical use act only on Ambler Class A, C and some class D lactamases. The urgent need to identify new BLIs recently lead to FDA approval of boron-based compounds BLIs, e.g. Vaborbactam. The boron-based proteasome inhibitors Bortezomib and Ixazomib are used in cancer therapy as multiple myeloma drugs but they also bind to Ser-/Thr- proteases. In this study we show the crystal structures of the beta-lactamase CTX-M-14 with covalently bound Bortezomib and Ixazomib at high resolutions of 1.3 and 1.1 A, respectively. Ixazomib is well defined in electron density whereas Bortezomib show some disorder which corresponds to weaker inhibition efficiency observed for Ixazomib. Both inhibitors mimic the deacylation transition state of beta-lactam hydrolysis, because they replace the deacylating water molecule. We further investigate differences in binding of Bortezomib/Ixazomib to CTX-M-14 and its target proteases as well as known beta-lactamase drugs. Our findings can help to use Bortezomib/Ixazomib as lead compounds for development of new BLIs. | ||
| + | |||
| + | Structural basis to repurpose boron-based proteasome inhibitors Bortezomib and Ixazomib as beta-lactamase inhibitors.,Perbandt M, Werner N, Prester A, Rohde H, Aepfelbacher M, Hinrichs W, Betzel C Sci Rep. 2022 Apr 1;12(1):5510. doi: 10.1038/s41598-022-09392-6. PMID:35365689<ref>PMID:35365689</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7q0y" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Klebsiella pneumoniae]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Aepfelbacher M]] | [[Category: Aepfelbacher M]] | ||
Revision as of 13:12, 1 February 2024
Crystal structure of CTX-M-14 in complex with Bortezomib
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