7mqm
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7mqm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MQM FirstGlance]. <br> | <table><tr><td colspan='2'>[[7mqm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MQM FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=51G:GENTAMICIN+C1'>51G</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=51G:GENTAMICIN+C1'>51G</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=7mqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mqm OCA], [https://pdbe.org/7mqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mqm RCSB], [https://www.ebi.ac.uk/pdbsum/7mqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mqm 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=7mqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mqm OCA], [https://pdbe.org/7mqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mqm RCSB], [https://www.ebi.ac.uk/pdbsum/7mqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mqm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/AACC3_PSEAI AACC3_PSEAI] Resistance to antibiotics containing the 2-deoxy-streptamine ring including dibekacin, gentamicin, kanamycin, sisomicin, tobramycin and neomycin, but not to amikacin or netilmicin (PubMed:1649572). Acetylates a broad range of both 4,5- and 4,6-disubstituted aminoglycosides, including neomycin, paromomycin, ribostamycin, sisomicin, gentamicin, tobramycin and kanamycin, with no preference of one disubstitution over the other. Acetylates sisomicin and kanamycin most and least efficiently, respectively. Does not modify plazomicin (PubMed:35921328).<ref>PMID:1649572</ref> <ref>PMID:35921328</ref> | |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Canonical aminoglycosides are a large group of antibiotics, where the part of chemical diversity stems from the substitution of the neamine ring system on positions 5 and 6. Certain aminoglycoside modifying enzymes can modify a broad range of 4,5- and 4,6-disubstituted aminoglycosides, with some as many as 15. This study presents the structural and kinetic results describing a promiscuous aminoglycoside acetyltransferase AAC(3)-IIIa. This enzyme has been crystallized in ternary complex with coenzyme A and 4,5- and 4,6-disubstituted aminoglycosides. We have followed up this work with kinetic characterization utilizing a panel of diverse aminoglycosides, including a next-generation aminoglycoside, plazomicin. Lastly, we observed an alternative binding mode of gentamicin in the aminoglycoside binding site, which was proven to be a crystallographic artifact based on mutagenesis. | Canonical aminoglycosides are a large group of antibiotics, where the part of chemical diversity stems from the substitution of the neamine ring system on positions 5 and 6. Certain aminoglycoside modifying enzymes can modify a broad range of 4,5- and 4,6-disubstituted aminoglycosides, with some as many as 15. This study presents the structural and kinetic results describing a promiscuous aminoglycoside acetyltransferase AAC(3)-IIIa. This enzyme has been crystallized in ternary complex with coenzyme A and 4,5- and 4,6-disubstituted aminoglycosides. We have followed up this work with kinetic characterization utilizing a panel of diverse aminoglycosides, including a next-generation aminoglycoside, plazomicin. Lastly, we observed an alternative binding mode of gentamicin in the aminoglycoside binding site, which was proven to be a crystallographic artifact based on mutagenesis. | ||
| - | Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa.,Zielinski M, Blanchet J, Hailemariam S, Berghuis AM PLoS One. 2022 Aug 3;17(8):e0269684. doi: 10.1371/journal.pone.0269684., eCollection 2022. PMID:35921328<ref>PMID:35921328</ref> | + | Structural elucidation of substrate-bound aminoglycoside acetyltransferase (3)-IIIa.,Zielinski M, Blanchet J, Hailemariam S, Berghuis AM PLoS One. 2022 Aug 3;17(8):e0269684. doi: 10.1371/journal.pone.0269684. , eCollection 2022. PMID:35921328<ref>PMID:35921328</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
AAC(3)-IIIa in complex with CoA and gentamicin
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