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| | ==Crystal Structure of 16S rRNA Methyltranferase== | | ==Crystal Structure of 16S rRNA Methyltranferase== |
| - | <StructureSection load='3mte' size='340' side='right' caption='[[3mte]], [[Resolution|resolution]] 1.81Å' scene=''> | + | <StructureSection load='3mte' size='340' side='right'caption='[[3mte]], [[Resolution|resolution]] 1.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mte]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MTE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MTE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mte]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MTE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MTE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mq2|3mq2]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3mq2|3mq2]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">npmA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">npmA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=3mte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mte OCA], [http://pdbe.org/3mte PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mte RCSB], [http://www.ebi.ac.uk/pdbsum/3mte PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mte 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=3mte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mte OCA], [https://pdbe.org/3mte PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mte RCSB], [https://www.ebi.ac.uk/pdbsum/3mte PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mte ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NPMA_ECOLX NPMA_ECOLX]] Specifically methylates the N(1) position of adenine 1408 in 16S rRNA. Confers resistance to various aminoglycosides, including kanamycin, neomycin, apramycin, ribostamycin and gentamicin. Methylates only fully assembled 30S subunits.<ref>PMID:17875999</ref> <ref>PMID:20667473</ref> <ref>PMID:21062819</ref> | + | [[https://www.uniprot.org/uniprot/NPMA_ECOLX NPMA_ECOLX]] Specifically methylates the N(1) position of adenine 1408 in 16S rRNA. Confers resistance to various aminoglycosides, including kanamycin, neomycin, apramycin, ribostamycin and gentamicin. Methylates only fully assembled 30S subunits.<ref>PMID:17875999</ref> <ref>PMID:20667473</ref> <ref>PMID:21062819</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bacillus coli migula 1895]] | | [[Category: Bacillus coli migula 1895]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Conn, G L]] | | [[Category: Conn, G L]] |
| | [[Category: Macmaster, R A]] | | [[Category: Macmaster, R A]] |
| Structural highlights
Function
[NPMA_ECOLX] Specifically methylates the N(1) position of adenine 1408 in 16S rRNA. Confers resistance to various aminoglycosides, including kanamycin, neomycin, apramycin, ribostamycin and gentamicin. Methylates only fully assembled 30S subunits.[1] [2] [3]
Publication Abstract from PubMed
X-ray crystal structures were determined of the broad-spectrum aminoglycoside-resistance A1408 16S rRNA methyltransferases KamB and NpmA, from the aminoglycoside-producer Streptoalloteichus tenebrarius and human pathogenic Escherichia coli, respectively. Consistent with their common function, both are Class I methyltransferases with additional highly conserved structural motifs that embellish the core SAM-binding fold. In overall structure, the A1408 rRNA methyltransferase were found to be most similar to a second family of Class I methyltransferases of distinct substrate specificity (m(7)G46 tRNA). Critical residues for A1408 rRNA methyltransferase activity were experimentally defined using protein mutagenesis and bacterial growth assays with kanamycin. Essential residues for SAM coenzyme binding and an extended protein surface that likely interacts with the 30S ribosomal subunit were thus revealed. The structures also suggest potential mechanisms of A1408 target nucleotide selection and positioning. We propose that a dynamic extended loop structure that is positioned adjacent to both the bound SAM and a functionally critical structural motif may mediate concerted conformational changes in rRNA and protein that underpin the specificity of target selection and activation of methyltransferase activity. These new structures provide important new insights that may provide a starting point for strategies to inhibit these emerging causes of pathogenic bacterial resistance to aminoglycosides.
Structural insights into the function of aminoglycoside-resistance A1408 16S rRNA methyltransferases from antibiotic-producing and human pathogenic bacteria.,Macmaster R, Zelinskaya N, Savic M, Rankin CR, Conn GL Nucleic Acids Res. 2010 Nov 1;38(21):7791-9. Epub 2010 Jul 17. PMID:20639535[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wachino J, Shibayama K, Kurokawa H, Kimura K, Yamane K, Suzuki S, Shibata N, Ike Y, Arakawa Y. Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Antimicrob Agents Chemother. 2007 Dec;51(12):4401-9. Epub 2007 Sep 17. PMID:17875999 doi:http://dx.doi.org/10.1128/AAC.00926-07
- ↑ Zelinskaya N, Rankin CR, Macmaster R, Savic M, Conn GL. Expression, purification and crystallization of adenosine 1408 aminoglycoside-resistance rRNA methyltransferases for structural studies. Protein Expr Purif. 2011 Jan;75(1):89-94. doi: 10.1016/j.pep.2010.07.005. Epub, 2010 Jul 25. PMID:20667473 doi:http://dx.doi.org/10.1016/j.pep.2010.07.005
- ↑ Husain N, Obranic S, Koscinski L, Seetharaman J, Babic F, Bujnicki JM, Maravic-Vlahovicek G, Sivaraman J. Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit. Nucleic Acids Res. 2010 Nov 9. PMID:21062819 doi:10.1093/nar/gkq1033
- ↑ Macmaster R, Zelinskaya N, Savic M, Rankin CR, Conn GL. Structural insights into the function of aminoglycoside-resistance A1408 16S rRNA methyltransferases from antibiotic-producing and human pathogenic bacteria. Nucleic Acids Res. 2010 Nov 1;38(21):7791-9. Epub 2010 Jul 17. PMID:20639535 doi:10.1093/nar/gkq627
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