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==Crystal structure of aminoglycoside acetyltransferase AAC(3)-Xa== | ==Crystal structure of aminoglycoside acetyltransferase AAC(3)-Xa== | ||
<StructureSection load='7lap' size='340' side='right'caption='[[7lap]]' scene=''> | <StructureSection load='7lap' size='340' side='right'caption='[[7lap]], [[Resolution|resolution]] 2.04Å' 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=7LAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LAP FirstGlance]. <br> | <table><tr><td colspan='2'>[[7lap]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"actinomyces_griseus"_krainsky_1914 "actinomyces griseus" krainsky 1914]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LAP 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=7lap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lap OCA], [https://pdbe.org/7lap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lap RCSB], [https://www.ebi.ac.uk/pdbsum/7lap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lap 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">kan, yokD_2, NCTC13033_06639 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1911 "Actinomyces griseus" Krainsky 1914])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aminoglycoside_N(3')-acetyltransferase Aminoglycoside N(3')-acetyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.81 2.3.1.81] </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=7lap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lap OCA], [https://pdbe.org/7lap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lap RCSB], [https://www.ebi.ac.uk/pdbsum/7lap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lap ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment. | |||
Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family.,Stogios PJ, Bordeleau E, Xu Z, Skarina T, Evdokimova E, Chou S, Diorio-Toth L, D'Souza AW, Patel S, Dantas G, Wright GD, Savchenko A Commun Biol. 2022 Mar 25;5(1):263. doi: 10.1038/s42003-022-03219-w. PMID:35338238<ref>PMID:35338238</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7lap" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Actinomyces griseus krainsky 1914]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: Joachimiak A]] | [[Category: Joachimiak, A]] | ||
[[Category: Kim Y]] | [[Category: Kim, Y]] | ||
[[Category: Satchell | [[Category: Leo, R Di]] | ||
[[Category: Savchenko A]] | [[Category: Satchell, K J.F]] | ||
[[Category: Skarina T]] | [[Category: Savchenko, A]] | ||
[[Category: Stogios | [[Category: Skarina, T]] | ||
[[Category: Stogios, P J]] | |||
[[Category: Csgid]] | |||
[[Category: National institute of allergy and infectious disease]] | |||
[[Category: Niaid]] | |||
[[Category: Resistance]] | |||
[[Category: Transferase]] | |||
Revision as of 13:32, 6 April 2022
Crystal structure of aminoglycoside acetyltransferase AAC(3)-XaCrystal structure of aminoglycoside acetyltransferase AAC(3)-Xa
Structural highlights
Publication Abstract from PubMedThe environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment. Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family.,Stogios PJ, Bordeleau E, Xu Z, Skarina T, Evdokimova E, Chou S, Diorio-Toth L, D'Souza AW, Patel S, Dantas G, Wright GD, Savchenko A Commun Biol. 2022 Mar 25;5(1):263. doi: 10.1038/s42003-022-03219-w. PMID:35338238[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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