7rpf
From Proteopedia
(Difference between revisions)
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==X-ray crystal structure of OXA-24/40 in complex with doripenem== | ==X-ray crystal structure of OXA-24/40 in complex with doripenem== | ||
- | <StructureSection load='7rpf' size='340' side='right'caption='[[7rpf]]' scene=''> | + | <StructureSection load='7rpf' size='340' side='right'caption='[[7rpf]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RPF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7rpf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RPF FirstGlance]. <br> |
- | </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=7rpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpf OCA], [https://pdbe.org/7rpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpf RCSB], [https://www.ebi.ac.uk/pdbsum/7rpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpf ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4J6:(4R,5S)-5-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-4-METHYL-3-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>4J6</scene>, <scene name='pdbligand=BCT:BICARBONATE+ION'>BCT</scene>, <scene name='pdbligand=DRW:(2S,3R,4S)-2-[(2S,3R)-3-HYDROXY-1-OXOBUTAN-2-YL]-3-METHYL-4-({(3S,5S)-5-[(SULFAMOYLAMINO)METHYL]PYRROLIDIN-3-YL}SULFANYL)-3,4-DIHYDRO-2H-PYRROLE-5-CARBOXYLIC+ACID'>DRW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
+ | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | ||
+ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://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=7rpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpf OCA], [https://pdbe.org/7rpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpf RCSB], [https://www.ebi.ac.uk/pdbsum/7rpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | The evolution of multidrug resistance (MDR) in Acinetobacter spp. increases the risk of our best antibiotics losing their efficacy. From a clinical perspective, the carbapenem-hydrolyzing class D beta-lactamase (CHDL) subfamily present in Acetinobacter spp. is particularly concerning due to its ability to confer resistance to carbapenems. The kinetic profiles of class D beta-lactamases exhibit variability in carbapenem hydrolysis, suggesting functional differences. To better understand the structure-function relationship between the CHDL OXA-24/40 found in A. baumannii and carbapenem substrates, we analyzed steady-state kinetics with the carbapenem antibiotics meropenem and ertapenem, and determined the structures of complexes of OXA-24/40 bound to imipenem, meropenem, doripenem, and ertapenem, as well as the expanded-spectrum cephalosporin cefotaxime, using X-ray crystallography. We show that OXA-24/40 exhibits a preference for ertapenem compared to meropenem, imipenem, and doripenem, with an increase in catalytic efficiency of up to four-fold. We suggest that superposition of the nine OXA-24/40 complexes will better inform future inhibitor design efforts by providing insight into the complicated and varying ways in which carbapenems are selected and bound by class D beta-lactamases. | ||
+ | |||
+ | Conformational flexibility in carbapenem hydrolysis drives substrate specificity of the class D carbapenemase OXA-24/40.,Mitchell JM, June CM, Baggett VL, Lowe BC, Ruble JF, Bonomo RA, Leonard DA, Powers RA J Biol Chem. 2022 Jun 13:102127. doi: 10.1016/j.jbc.2022.102127. PMID:35709986<ref>PMID:35709986</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 7rpf" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] | *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
+ | [[Category: Beta-lactamase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
- | [[Category: June | + | [[Category: June, C M]] |
- | [[Category: Mitchell | + | [[Category: Mitchell, J M]] |
- | [[Category: Powers | + | [[Category: Powers, R A]] |
+ | [[Category: Acyl-enzyme complex]] | ||
+ | [[Category: Carbapenemase]] | ||
+ | [[Category: Hydrolase]] | ||
+ | [[Category: Hydrolase-inhibitor complex]] |
Revision as of 18:17, 27 July 2022
X-ray crystal structure of OXA-24/40 in complex with doripenem
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