6vr3
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==Aminoglycoside N-2'-Acetyltransferase-Ia [AAC(2')-Ia] in complex with acetylated-netilmicin and CoA== | ==Aminoglycoside N-2'-Acetyltransferase-Ia [AAC(2')-Ia] in complex with acetylated-netilmicin and CoA== | ||
| - | <StructureSection load='6vr3' size='340' side='right'caption='[[6vr3]]' scene=''> | + | <StructureSection load='6vr3' size='340' side='right'caption='[[6vr3]], [[Resolution|resolution]] 2.00Å' 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=6VR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VR3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vr3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Providencia_stuartii Providencia stuartii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VR3 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=6vr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vr3 OCA], [https://pdbe.org/6vr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vr3 RCSB], [https://www.ebi.ac.uk/pdbsum/6vr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vr3 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=NTL:N-[(2S,3R)-2-{[(1R,2S,3S,4R,6S)-6-amino-3-{[3-deoxy-4-C-methyl-3-(methylamino)-beta-L-lyxopyranosyl]oxy}-4-(ethylamino)+-2-hydroxycyclohexyl]oxy}-6-(aminomethyl)-3,4-dihydro-2H-pyran-3-yl]acetamide'>NTL</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=6vr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vr3 OCA], [https://pdbe.org/6vr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vr3 RCSB], [https://www.ebi.ac.uk/pdbsum/6vr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vr3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AAC2_PROST AAC2_PROST] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Plazomicin is currently the only next-generation aminoglycoside approved for clinical use that has the potential of evading the effects of widespread enzymatic resistance factors. However, plazomicin is still susceptible to the action of the resistance enzyme AAC(2')-Ia from Providencia stuartii. As the clinical use of plazomicin begins to increase, the spread of resistance factors will undoubtedly accelerate, rendering this aminoglycoside increasingly obsolete. Understanding resistance to plazomicin is an important step to ensure this aminoglycoside remains a viable treatment option for the foreseeable future. Here, we present three crystal structures of AAC(2')-Ia from P. stuartii, two in complex with acetylated aminoglycosides tobramycin and netilmicin, and one in complex with a non-substrate aminoglycoside, amikacin. Together, with our previously reported AAC(2')-Ia-acetylated plazomicin complex, these structures outline AAC(2')-Ia's specificity for a wide range of aminoglycosides. Additionally, our survey of AAC(2')-I homologues highlights the conservation of residues predicted to be involved in aminoglycoside binding, and identifies the presence of plasmid-encoded enzymes in environmental strains that confer resistance to the latest next-generation aminoglycoside. These results forecast the likely spread of plazomicin resistance and highlight the urgency for advancements in next-generation aminoglycoside design. | ||
| + | |||
| + | Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2') enzymes.,Bassenden AV, Dumalo L, Park J, Blanchet J, Maiti K, Arya DP, Berghuis AM Sci Rep. 2021 Jun 2;11(1):11614. doi: 10.1038/s41598-021-89446-3. PMID:34078922<ref>PMID:34078922</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6vr3" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Providencia stuartii]] | ||
[[Category: Bassenden AV]] | [[Category: Bassenden AV]] | ||
[[Category: Berghuis AM]] | [[Category: Berghuis AM]] | ||
Current revision
Aminoglycoside N-2'-Acetyltransferase-Ia [AAC(2')-Ia] in complex with acetylated-netilmicin and CoA
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