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==Crystal Structure of the Di-Zinc Carbapenemase CphA from Aeromonas Hydrophila== | |||
<StructureSection load='3f9o' size='340' side='right'caption='[[3f9o]], [[Resolution|resolution]] 2.03Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3f9o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aeromonas_hydrophila Aeromonas hydrophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F9O 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]] 2.03Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3f9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f9o OCA], [https://pdbe.org/3f9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f9o RCSB], [https://www.ebi.ac.uk/pdbsum/3f9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f9o ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLAB_AERHY BLAB_AERHY] Can hydrolyze carbapenem compounds. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f9/3f9o_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3f9o ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bacteria can defend themselves against beta-lactam antibiotics through the expression of class B beta-lactamases, which cleave the beta-lactam amide bond and render the molecule harmless. There are three subclasses of class B beta-lactamases (B1, B2, and B3), all of which require Zn2+ for activity and can bind either one or two zinc ions. Whereas the B1 and B3 metallo-beta-lactamases are most active as dizinc enzymes, subclass B2 enzymes, such as Aeromonas hydrophila CphA, are inhibited by the binding of a second zinc ion. We crystallized A. hydrophila CphA in order to determine the binding site of the inhibitory zinc ion. X-ray data from zinc-saturated crystals allowed us to solve the crystal structures of the dizinc forms of the wild-type enzyme and N220G mutant. The first zinc ion binds in the cysteine site, as previously determined for the monozinc form of the enzyme. The second zinc ion occupies a slightly modified histidine site, where the conserved His118 and His196 residues act as metal ligands. This atypical coordination sphere probably explains the rather high dissociation constant for the second zinc ion compared to those observed with enzymes of subclasses B1 and B3. Inhibition by the second zinc ion results from immobilization of the catalytically important His118 and His196 residues, as well as the folding of the Gly232-Asn233 loop into a position that covers the active site. | |||
The structure of the dizinc subclass B2 metallo-beta-lactamase CphA reveals that the second inhibitory zinc ion binds in the histidine site.,Bebrone C, Delbruck H, Kupper MB, Schlomer P, Willmann C, Frere JM, Fischer R, Galleni M, Hoffmann KM Antimicrob Agents Chemother. 2009 Oct;53(10):4464-71. Epub 2009 Aug 3. PMID:19651913<ref>PMID:19651913</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3f9o" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Aeromonas hydrophila]] | [[Category: Aeromonas hydrophila]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Delbruck | [[Category: Delbruck H]] | ||
[[Category: Hoffmann | [[Category: Hoffmann KMV]] | ||
Latest revision as of 18:28, 1 November 2023
Crystal Structure of the Di-Zinc Carbapenemase CphA from Aeromonas HydrophilaCrystal Structure of the Di-Zinc Carbapenemase CphA from Aeromonas Hydrophila
Structural highlights
FunctionBLAB_AERHY Can hydrolyze carbapenem compounds. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBacteria can defend themselves against beta-lactam antibiotics through the expression of class B beta-lactamases, which cleave the beta-lactam amide bond and render the molecule harmless. There are three subclasses of class B beta-lactamases (B1, B2, and B3), all of which require Zn2+ for activity and can bind either one or two zinc ions. Whereas the B1 and B3 metallo-beta-lactamases are most active as dizinc enzymes, subclass B2 enzymes, such as Aeromonas hydrophila CphA, are inhibited by the binding of a second zinc ion. We crystallized A. hydrophila CphA in order to determine the binding site of the inhibitory zinc ion. X-ray data from zinc-saturated crystals allowed us to solve the crystal structures of the dizinc forms of the wild-type enzyme and N220G mutant. The first zinc ion binds in the cysteine site, as previously determined for the monozinc form of the enzyme. The second zinc ion occupies a slightly modified histidine site, where the conserved His118 and His196 residues act as metal ligands. This atypical coordination sphere probably explains the rather high dissociation constant for the second zinc ion compared to those observed with enzymes of subclasses B1 and B3. Inhibition by the second zinc ion results from immobilization of the catalytically important His118 and His196 residues, as well as the folding of the Gly232-Asn233 loop into a position that covers the active site. The structure of the dizinc subclass B2 metallo-beta-lactamase CphA reveals that the second inhibitory zinc ion binds in the histidine site.,Bebrone C, Delbruck H, Kupper MB, Schlomer P, Willmann C, Frere JM, Fischer R, Galleni M, Hoffmann KM Antimicrob Agents Chemother. 2009 Oct;53(10):4464-71. Epub 2009 Aug 3. PMID:19651913[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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