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| | ==Crystal structure of AadA - an aminoglycoside adenyltransferase== | | ==Crystal structure of AadA - an aminoglycoside adenyltransferase== |
| - | <StructureSection load='4cs6' size='340' side='right' caption='[[4cs6]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4cs6' size='340' side='right'caption='[[4cs6]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cs6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Salty Salty]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CS6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CS6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cs6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium_str._LT2 Salmonella enterica subsp. enterica serovar Typhimurium str. LT2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CS6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CS6 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cs6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cs6 OCA], [http://pdbe.org/4cs6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cs6 RCSB], [http://www.ebi.ac.uk/pdbsum/4cs6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cs6 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=4cs6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cs6 OCA], [https://pdbe.org/4cs6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cs6 RCSB], [https://www.ebi.ac.uk/pdbsum/4cs6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cs6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [[https://www.uniprot.org/uniprot/S3AD_SALTY S3AD_SALTY]] Mediates bacterial resistance to the antibiotics streptomycin and spectinomycin, does not confer resistance to kanamycin (PubMed:26527143). Binds ATP first, then antibiotic (PubMed:26527143, PubMed:29871922).<ref>PMID:26527143</ref> <ref>PMID:29871922</ref> |
| | <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: Salty]] | + | [[Category: Large Structures]] |
| - | [[Category: Andersson, D I]] | + | [[Category: Salmonella enterica subsp. enterica serovar Typhimurium str. LT2]] |
| - | [[Category: Chen, Y]] | + | [[Category: Andersson DI]] |
| - | [[Category: Nasvall, J]] | + | [[Category: Chen Y]] |
| - | [[Category: Selmer, M]] | + | [[Category: Nasvall J]] |
| - | [[Category: Aminoglycoside adenyltransferase]]
| + | [[Category: Selmer M]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
[S3AD_SALTY] Mediates bacterial resistance to the antibiotics streptomycin and spectinomycin, does not confer resistance to kanamycin (PubMed:26527143). Binds ATP first, then antibiotic (PubMed:26527143, PubMed:29871922).[1] [2]
Publication Abstract from PubMed
Aminoglycoside resistance is commonly conferred by enzymatic modification of drugs by aminoglycoside-modifying enzymes such as aminoglycoside nucleotidyltransferases (ANTs). Here, the first crystal structure of an ANT(3)(9) adenyltransferase, AadA from Salmonella enterica, is presented. AadA catalyses the magnesium-dependent transfer of adenosine monophosphate from ATP to the two chemically dissimilar drugs streptomycin and spectinomycin. The structure was solved using selenium SAD phasing and refined to 2.5 A resolution. AadA consists of a nucleotidyltransferase domain and an alpha-helical bundle domain. AadA crystallizes as a monomer and is a monomer in solution as confirmed by small-angle X-ray scattering, in contrast to structurally similar homodimeric adenylating enzymes such as kanamycin nucleotidyltransferase. Isothermal titration calorimetry experiments show that ATP binding has to occur before binding of the aminoglycoside substrate, and structure analysis suggests that ATP binding repositions the two domains for aminoglycoside binding in the interdomain cleft. Candidate residues for ligand binding and catalysis were subjected to site-directed mutagenesis. In vivo resistance and in vitro binding assays support the role of Glu87 as the catalytic base in adenylation, while Arg192 and Lys205 are shown to be critical for ATP binding.
Structure of AadA from Salmonella enterica: a monomeric aminoglycoside (3)(9) adenyltransferase.,Chen Y, Nasvall J, Wu S, Andersson DI, Selmer M Acta Crystallogr D Biol Crystallogr. 2015 Nov 1;71(Pt 11):2267-77. doi:, 10.1107/S1399004715016429. Epub 2015 Oct 31. PMID:26527143[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen Y, Nasvall J, Wu S, Andersson DI, Selmer M. Structure of AadA from Salmonella enterica: a monomeric aminoglycoside (3)(9) adenyltransferase. Acta Crystallogr D Biol Crystallogr. 2015 Nov 1;71(Pt 11):2267-77. doi:, 10.1107/S1399004715016429. Epub 2015 Oct 31. PMID:26527143 doi:http://dx.doi.org/10.1107/S1399004715016429
- ↑ Stern AL, Van der Verren SE, Kanchugal P S, Nasvall J, Gutierrez de Teran H, Selmer M. Structural mechanism of AadA, a dual specificity aminoglycoside adenyl transferase from Salmonella enterica. J Biol Chem. 2018 Jun 5. pii: RA118.003989. doi: 10.1074/jbc.RA118.003989. PMID:29871922 doi:http://dx.doi.org/10.1074/jbc.RA118.003989
- ↑ Chen Y, Nasvall J, Wu S, Andersson DI, Selmer M. Structure of AadA from Salmonella enterica: a monomeric aminoglycoside (3)(9) adenyltransferase. Acta Crystallogr D Biol Crystallogr. 2015 Nov 1;71(Pt 11):2267-77. doi:, 10.1107/S1399004715016429. Epub 2015 Oct 31. PMID:26527143 doi:http://dx.doi.org/10.1107/S1399004715016429
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