7q11: Difference between revisions
New page: '''Unreleased structure''' The entry 7q11 is ON HOLD Authors: Werner, N., Perbandt, M., Hinrichs, W., Prester, A., Rohde, H., Aepfelbacher, M., Betzel, C. Description: Crystal structur... |
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The | ==Crystal structure of CTX-M-14 in complex with Ixazomib== | ||
<StructureSection load='7q11' size='340' side='right'caption='[[7q11]], [[Resolution|resolution]] 1.14Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q11 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q11 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]] 1.14Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6V8:[(1~{R})-1-[2-[[2,5-BIS(CHLORANYL)PHENYL]CARBONYLAMINO]ETHANOYLAMINO]-3-METHYL-BUTYL]BORONIC+ACID'>6V8</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=7q11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q11 OCA], [https://pdbe.org/7q11 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q11 RCSB], [https://www.ebi.ac.uk/pdbsum/7q11 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q11 ProSAT]</span></td></tr> | |||
</table> | |||
<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> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7q11" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
[[Category: Prester | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Aepfelbacher M]] | |||
[[Category: Betzel C]] | |||
[[Category: Hinrichs W]] | |||
[[Category: Perbandt M]] | |||
[[Category: Prester A]] | |||
[[Category: Rohde H]] | |||
[[Category: Werner N]] | |||