5iy2: Difference between revisions
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==Structure of apo OXA-143 carbapenemase== | ==Structure of apo OXA-143 carbapenemase== | ||
<StructureSection load='5iy2' size='340' side='right' caption='[[5iy2]], [[Resolution|resolution]] 1.15Å' scene=''> | <StructureSection load='5iy2' size='340' side='right'caption='[[5iy2]], [[Resolution|resolution]] 1.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5iy2]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5iy2]] is a 2 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=5IY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IY2 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]] 1.15Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</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=5iy2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iy2 OCA], [https://pdbe.org/5iy2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iy2 RCSB], [https://www.ebi.ac.uk/pdbsum/5iy2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iy2 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/D0UHC8_ACIBA D0UHC8_ACIBA] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Acinetobacter baumannii]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Smith CA]] | ||
[[Category: | [[Category: Vakulenko SB]] | ||
Latest revision as of 13:37, 6 September 2023
Structure of apo OXA-143 carbapenemaseStructure of apo OXA-143 carbapenemase
Structural highlights
FunctionPublication Abstract from PubMedCarbapenem-hydrolyzing class D beta-lactamases (CHDLs) produce resistance to the last-resort carbapenem antibiotics and render these drugs ineffective for the treatment of life-threatening infections. Here, it is shown that among the clinically important CHDLs, OXA-143 produces the highest levels of resistance to carbapenems and has the highest catalytic efficiency against these substrates. Structural data demonstrate that acylated carbapenems entirely fill the active site of CHDLs, leaving no space for water molecules, including the deacylating water. Since the entrance to the active site is obstructed by the acylated antibiotic, the deacylating water molecule must take a different route for entry. It is shown that in OXA-143 the movement of a conserved hydrophobic valine residue on the surface opens a channel to the active site of the enzyme, which would not only allow the exchange of water molecules between the active site and the milieu, but would also create extra space for a water molecule to position itself in the vicinity of the scissile bond of the acyl-enzyme intermediate to perform deacylation. Structural analysis of the OXA-23 carbapenemase shows that in this enzyme movement of the conserved leucine residue, juxtaposed to the valine on the molecular surface, creates a similar channel to the active site. These data strongly suggest that all CHDLs may employ a mechanism whereupon the movement of highly conserved valine or leucine residues would allow a water molecule to access the active site to promote deacylation. It is further demonstrated that the 6alpha-hydroxyethyl group of the bound carbapenem plays an important role in the stabilization of this channel. The recognition of a universal deacylation mechanism for CHDLs suggests a direction for the future development of inhibitors and novel antibiotics for these enzymes of utmost clinical importance. The role of conserved surface hydrophobic residues in the carbapenemase activity of the class D beta-lactamases.,Toth M, Smith CA, Antunes NT, Stewart NK, Maltz L, Vakulenko SB Acta Crystallogr D Struct Biol. 2017 Aug 1;73(Pt 8):692-701. doi:, 10.1107/S2059798317008671. Epub 2017 Jul 28. PMID:28777084[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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