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| | <StructureSection load='7jzs' size='340' side='right'caption='[[7jzs]], [[Resolution|resolution]] 1.30Å' scene=''> | | <StructureSection load='7jzs' size='340' side='right'caption='[[7jzs]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7jzs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"proteus_stuartii"_buttiaux_et_al._1954 "proteus stuartii" buttiaux et al. 1954]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JZS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JZS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7jzs]] is a 1 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=7JZS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JZS FirstGlance]. <br> |
| - | </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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6vr3|6vr3]], [[6vr2|6vr2]], [[6vta|6vta]], [[6vou|6vou]]</div></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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aac ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=588 "Proteus stuartii" Buttiaux et al. 1954])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Gentamicin_2'-N-acetyltransferase Gentamicin 2'-N-acetyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.59 2.3.1.59] </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=7jzs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jzs OCA], [https://pdbe.org/7jzs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jzs RCSB], [https://www.ebi.ac.uk/pdbsum/7jzs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jzs ProSAT]</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=7jzs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jzs OCA], [https://pdbe.org/7jzs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jzs RCSB], [https://www.ebi.ac.uk/pdbsum/7jzs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jzs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/AAC2_PROST AAC2_PROST] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Proteus stuartii buttiaux et al. 1954]] | |
| - | [[Category: Gentamicin 2'-N-acetyltransferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bassenden, A V]] | + | [[Category: Providencia stuartii]] |
| - | [[Category: Berghuis, A M]] | + | [[Category: Bassenden AV]] |
| - | [[Category: Park, J]] | + | [[Category: Berghuis AM]] |
| - | [[Category: Acetyltransferase]] | + | [[Category: Park J]] |
| - | [[Category: Gnat superfamily]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
AAC2_PROST
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bassenden AV, Dumalo L, Park J, Blanchet J, Maiti K, Arya DP, Berghuis AM. Structural and phylogenetic analyses of resistance to next-generation aminoglycosides conferred by AAC(2') enzymes. Sci Rep. 2021 Jun 2;11(1):11614. doi: 10.1038/s41598-021-89446-3. PMID:34078922 doi:http://dx.doi.org/10.1038/s41598-021-89446-3
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