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6dgu
From Proteopedia
(Difference between revisions)
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<StructureSection load='6dgu' size='340' side='right'caption='[[6dgu]], [[Resolution|resolution]] 2.69Å' scene=''> | <StructureSection load='6dgu' size='340' side='right'caption='[[6dgu]], [[Resolution|resolution]] 2.69Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6dgu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DGU OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[6dgu]] 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=6DGU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DGU FirstGlance]. <br> |
| - | </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> | + | </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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | <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'>[http://proteopedia.org/fgij/fg.htm?mol=6dgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dgu OCA], [http://pdbe.org/6dgu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dgu RCSB], [http://www.ebi.ac.uk/pdbsum/6dgu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dgu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:31235626</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6dgu" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacterium freundii braak 1928]] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
Revision as of 06:31, 3 June 2020
PER-2 class A extended-spectrum beta-lactamase crystal structure at 2.69 Angstrom resolution
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