6pwm: Difference between revisions
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<StructureSection load='6pwm' size='340' side='right'caption='[[6pwm]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='6pwm' size='340' side='right'caption='[[6pwm]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6pwm]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6pwm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PWM 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]] 2.4Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAZ:ACYLATED+CEFTAZIDIME'>CAZ</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</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=6pwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pwm OCA], [https://pdbe.org/6pwm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pwm RCSB], [https://www.ebi.ac.uk/pdbsum/6pwm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pwm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6DRA1_ACIBA Q6DRA1_ACIBA] | |||
<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 6pwm" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6pwm" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Acinetobacter baumannii]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Curtis | [[Category: Curtis BC]] | ||
[[Category: Powers | [[Category: Powers RA]] | ||
[[Category: Wallar | [[Category: Wallar BJ]] | ||
Revision as of 10:37, 11 October 2023
ADC-7 in complex with Beta-lactam antibiotic ceftazidimeADC-7 in complex with Beta-lactam antibiotic ceftazidime
Structural highlights
FunctionPublication Abstract from PubMedExtended-spectrum class C beta-lactamases have evolved to rapidly inactivate expanded spectrum cephalosporins, a class of antibiotics designed to be resistant to hydrolysis by beta-lactamase enzymes. To better understand the mechanism by which Acinetobacter-derived cephalosporinase-7 (ADC-7), a chromosomal AmpC enzyme, hydrolyzes these molecules, we determined the X-ray crystal structure of ADC-7 in an acyl-enzyme complex with the cephalosporin, ceftazidime (2.40 A), as well as in complex with a boronic acid transition state analog inhibitor that contains the R1 side chain of ceftazidime (1.67 A). In the acyl-enzyme complex, the carbonyl oxygen is situated in the oxyanion hole where it makes key stabilizing interactions with the main chain nitrogens of Ser64 and Ser315. The boronic acid O1 hydroxyl group is similarly positioned in this area. Conserved residues Gln120 and Asn152 form hydrogen bonds with the amide group of the R1 side chain in both complexes. These complexes represent two steps in the hydrolysis of expanded spectrum cephalosporins by ADC-7 and offer insight into the inhibition of ADC-7 by ceftazidime through displacement of the deacylating water molecule, as well as blocking its trajectory to the acyl carbonyl carbon. In addition, the transition state analog inhibitor, LP06, was shown to bind with high affinity to ADC-7 (K i 50 nM) and was able to restore ceftazidime susceptibility, offering the potential for optimization efforts of this type of inhibitor. Structural insights into inhibition of the Acinetobacter derived cephalosporinase ADC-7 by ceftazidime and its boronic acid transition state analog.,Curtis BN, Smolen KA, Barlow SJ, Caselli E, Prati F, Taracila MA, Bonomo RA, Wallar BJ, Powers RA Antimicrob Agents Chemother. 2020 Sep 28. pii: AAC.01183-20. doi:, 10.1128/AAC.01183-20. PMID:32988830[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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