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| | <StructureSection load='6d3g' size='340' side='right'caption='[[6d3g]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='6d3g' size='340' side='right'caption='[[6d3g]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d3g]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_freundii"_braak_1928 "bacterium freundii" braak 1928]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d3g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Citrobacter_freundii Citrobacter freundii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D3G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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]] 2.398Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaPER-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=546 "Bacterium freundii" Braak 1928])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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=6d3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3g OCA], [https://pdbe.org/6d3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d3g RCSB], [https://www.ebi.ac.uk/pdbsum/6d3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3g ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6d3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3g OCA], [http://pdbe.org/6d3g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3g RCSB], [http://www.ebi.ac.uk/pdbsum/6d3g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A2RP81_CITFR A2RP81_CITFR] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6d3g" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6d3g" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacterium freundii braak 1928]] | + | [[Category: Citrobacter freundii]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bonomo, R]] | + | [[Category: Bonomo R]] |
| - | [[Category: Gutkind, G]] | + | [[Category: Gutkind G]] |
| - | [[Category: Klinke, S]] | + | [[Category: Klinke S]] |
| - | [[Category: Power, P]] | + | [[Category: Power P]] |
| - | [[Category: Ruggiero, M]] | + | [[Category: Ruggiero M]] |
| - | [[Category: Antibiotic resistance]]
| + | |
| - | [[Category: Dbo]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Penicilloil-serine-transferase]]
| + | |
| Structural highlights
Function
A2RP81_CITFR
Publication Abstract from PubMed
The diazabicyclooctane (DBO) avibactam (AVI) reversibly inactivates most serine-beta-lactamases. Previous investigations showed that inhibition constants of AVI toward class A PER-2 are reminiscent of values observed for class C and D beta-lactamases (i.e., k 2/K of approximately 10(3) M(-1) s(-1)) but lower than other class A beta-lactamases (i.e., k 2/K = 10(4) to 10(5) M(-1) s(-1)). Herein, biochemical and structural studies were conducted with PER-2 and AVI to explore these differences. Furthermore, biochemical studies on Arg220 and Thr237 variants with AVI were conducted to gain deeper insight into the mechanism of PER-2 inactivation. The main biochemical and structural observations revealed the following: (i) both amino-acid substitutions in Arg220 and the rich hydrophobic content in the active site hinder the binding of catalytic waters and acylation, impairing AVI inhibition; (ii) movement of Ser130 upon binding of AVI favors the formation of a hydrogen bond with the sulfate group of AVI; and (iii) the Thr237Ala substitution alters the AVI inhibition constants. The acylation constant (k 2/K) of PER-2 by AVI is primarily influenced by stabilizing hydrogen bonds involving AVI and important residues such as Thr237 and Arg220. (Variants in Arg220 demonstrate a dramatic reduction in k 2/K) We also observed that displacement of Ser130 side chain impairs AVI acylation, an observation not made in other extended-spectrum beta-lactamases (ESBLs). Comparatively, relebactam combined with a beta-lactam is more potent against Escherichia coli producing PER-2 variants than beta-lactam-AVI combinations. Our findings provide a rationale for evaluating the utility of the currently available DBO inhibitors against unique ESBLs like PER-2 and anticipate the effectiveness of these inhibitors toward variants that may eventually be selected upon AVI usage.
Structural Insights into the Inhibition of the Extended-Spectrum beta-Lactamase PER-2 by Avibactam.,Ruggiero M, Papp-Wallace KM, Brunetti F, Barnes MD, Bonomo RA, Gutkind G, Klinke S, Power P Antimicrob Agents Chemother. 2019 Aug 23;63(9). pii: AAC.00487-19. doi:, 10.1128/AAC.00487-19. Print 2019 Sep. PMID:31235626[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ruggiero M, Papp-Wallace KM, Brunetti F, Barnes MD, Bonomo RA, Gutkind G, Klinke S, Power P. Structural Insights into the Inhibition of the Extended-Spectrum beta-Lactamase PER-2 by Avibactam. Antimicrob Agents Chemother. 2019 Aug 23;63(9). pii: AAC.00487-19. doi:, 10.1128/AAC.00487-19. Print 2019 Sep. PMID:31235626 doi:http://dx.doi.org/10.1128/AAC.00487-19
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