6izc: Difference between revisions
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<StructureSection load='6izc' size='340' side='right'caption='[[6izc]], [[Resolution|resolution]] 1.55Å' scene=''> | <StructureSection load='6izc' size='340' side='right'caption='[[6izc]], [[Resolution|resolution]] 1.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6izc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IZC OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6izc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_parahaemolyticus Vibrio parahaemolyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IZC 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]] 1.55Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6izc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6izc OCA], [https://pdbe.org/6izc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6izc RCSB], [https://www.ebi.ac.uk/pdbsum/6izc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6izc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A3E1IK87_VIBPH A0A3E1IK87_VIBPH] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-Lactams are the most widely used antibiotics in treating bacterial infections. However, they are rarely applied in infections caused by Vibrio parahaemolyticus, as the bacterium is intrinsically resistant to penicillins by expressing beta-lactamase. Here we report structural characterization of the CARB beta-lactamase from V. parahaemolyticus (CARB-20). CARB-20 is a class A beta-lactamase, belonging to subclass A1 (containing 70STFKAL75, 130SDNTAANL137, 164RXEXXLN170, 231VGDKTG236, etc.), group LSBL2 (with the disulfide bridge C77-C123, motif 231IADRSGAG238 and R244). CARB-20 adopts a typical subclass A1 beta-lactamase fold consisting of two domains. Its active site is constituted by four conserved motifs, similar to that of known subclass A1 beta-lactamases. Analysis of the active site structure reveals its substrate preference for penicillin, ampicillin and carbenicillin but not for latterly developed cephalosporins. Meanwhile, beta-lactamase inhibitors such as clavulanate and sulbactam can well fit into the active site, supporting beta-lactams combined with beta-lactamase inhibitors as a potential approach for treating infection of V. parahaemolyticus. The residues around the active site show certain variations, which can be useful for specific inhibitor design. In the directed evolution experiment, CARB-20 exhibited plasticity in developing significant resistance to inhibitors by accumulated residue substitutions. Therefore, careful monitoring of enzyme mutations is necessary for successfully applying beta-lactam/beta-lactamase inhibitor combination therapy. Taken together, our results open up an avenue of inhibitor design targeting vibrio beta-lactamases, facilitating the application of beta-lactams in treating vibrio infections. | |||
Structural analysis of the CARB beta-lactamase from Vibrio parahaemolyticus facilitates application of the beta-lactam/beta-lactamase inhibitor therapy.,Li P, Liu C, Li B, Ma Q Biochimie. 2020 Apr - May;171-172:213-222. doi: 10.1016/j.biochi.2020.03.011., Epub 2020 Mar 13. PMID:32179166<ref>PMID:32179166</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6izc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Vibrio parahaemolyticus]] | ||
[[Category: | [[Category: Li P]] | ||
[[Category: | [[Category: Ma Q]] | ||
Latest revision as of 12:56, 22 November 2023
Crystal structure of the chromosome-encoded beta-lactamase of Vibrio parahaemolyticusCrystal structure of the chromosome-encoded beta-lactamase of Vibrio parahaemolyticus
Structural highlights
FunctionPublication Abstract from PubMedbeta-Lactams are the most widely used antibiotics in treating bacterial infections. However, they are rarely applied in infections caused by Vibrio parahaemolyticus, as the bacterium is intrinsically resistant to penicillins by expressing beta-lactamase. Here we report structural characterization of the CARB beta-lactamase from V. parahaemolyticus (CARB-20). CARB-20 is a class A beta-lactamase, belonging to subclass A1 (containing 70STFKAL75, 130SDNTAANL137, 164RXEXXLN170, 231VGDKTG236, etc.), group LSBL2 (with the disulfide bridge C77-C123, motif 231IADRSGAG238 and R244). CARB-20 adopts a typical subclass A1 beta-lactamase fold consisting of two domains. Its active site is constituted by four conserved motifs, similar to that of known subclass A1 beta-lactamases. Analysis of the active site structure reveals its substrate preference for penicillin, ampicillin and carbenicillin but not for latterly developed cephalosporins. Meanwhile, beta-lactamase inhibitors such as clavulanate and sulbactam can well fit into the active site, supporting beta-lactams combined with beta-lactamase inhibitors as a potential approach for treating infection of V. parahaemolyticus. The residues around the active site show certain variations, which can be useful for specific inhibitor design. In the directed evolution experiment, CARB-20 exhibited plasticity in developing significant resistance to inhibitors by accumulated residue substitutions. Therefore, careful monitoring of enzyme mutations is necessary for successfully applying beta-lactam/beta-lactamase inhibitor combination therapy. Taken together, our results open up an avenue of inhibitor design targeting vibrio beta-lactamases, facilitating the application of beta-lactams in treating vibrio infections. Structural analysis of the CARB beta-lactamase from Vibrio parahaemolyticus facilitates application of the beta-lactam/beta-lactamase inhibitor therapy.,Li P, Liu C, Li B, Ma Q Biochimie. 2020 Apr - May;171-172:213-222. doi: 10.1016/j.biochi.2020.03.011., Epub 2020 Mar 13. PMID:32179166[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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