View source for 7kes


==Crystal structure of meta-AAC0038, an environmental aminoglycoside resistance enzyme, mutant H168A in complex with apramycin and CoA==
<StructureSection load='7kes' size='340' side='right'caption='[[7kes]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kes]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Uncultured_bacterium Uncultured bacterium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KES 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]] 2.36&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AM2:APRAMYCIN'>AM2</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7kes FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kes OCA], [https://pdbe.org/7kes PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kes RCSB], [https://www.ebi.ac.uk/pdbsum/7kes PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kes ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A059X981_9BACT A0A059X981_9BACT] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kes" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Uncultured bacterium]]
[[Category: Joachimiak A]]
[[Category: Michalska K]]
[[Category: Satchell KJ]]
[[Category: Savchenko A]]
[[Category: Skarina T]]
[[Category: Stogios PJ]]
[[Category: Xu Z]]
[[Category: Yim V]]