This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6dgu
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6dgu is ON HOLD Authors: Power, P., Ruggiero, M., Gutkind, G., Bonomo, R., Klinke, S. Description: PER-2 class A extended-spectrum beta-lactamase c...) |
|||
| (6 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==PER-2 class A extended-spectrum beta-lactamase crystal structure at 2.69 Angstrom resolution== | |
| + | <StructureSection load='6dgu' size='340' side='right'caption='[[6dgu]], [[Resolution|resolution]] 2.69Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6dgu]] 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=6DGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DGU 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]] 2.691Å</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=6dgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dgu OCA], [https://pdbe.org/6dgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dgu RCSB], [https://www.ebi.ac.uk/pdbsum/6dgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dgu ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A2RP81_CITFR A2RP81_CITFR] | ||
| + | <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. | ||
| - | + | 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> | |
| - | [[Category: | + | </div> |
| - | [[Category: Bonomo | + | <div class="pdbe-citations 6dgu" style="background-color:#fffaf0;"></div> |
| - | [[Category: Gutkind | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Citrobacter freundii]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bonomo R]] | ||
| + | [[Category: Gutkind G]] | ||
| + | [[Category: Klinke S]] | ||
| + | [[Category: Power P]] | ||
| + | [[Category: Ruggiero M]] | ||
Current revision
PER-2 class A extended-spectrum beta-lactamase crystal structure at 2.69 Angstrom resolution
| |||||||||||
