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| | <StructureSection load='3lcu' size='340' side='right'caption='[[3lcu]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='3lcu' size='340' side='right'caption='[[3lcu]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lcu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"micromonospora_zionensis"_marquez_et_al. "micromonospora zionensis" marquez et al.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LCU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LCU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lcu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Micromonospora_zionensis Micromonospora zionensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LCU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 2.1Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3lcv|3lcv]]</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=3lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lcu OCA], [https://pdbe.org/3lcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lcu RCSB], [https://www.ebi.ac.uk/pdbsum/3lcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lcu ProSAT]</span></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=3lcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lcu OCA], [http://pdbe.org/3lcu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lcu RCSB], [http://www.ebi.ac.uk/pdbsum/3lcu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lcu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SGM_MICZI SGM_MICZI]] Specifically methylates the N(7) position of guanine 1405 in 16S rRNA. Confers resistance to various aminoglycosides, including gentamicin, kanamycin and sisomicin.<ref>PMID:1447159</ref> <ref>PMID:19589804</ref> | + | [https://www.uniprot.org/uniprot/SGM_MICZI SGM_MICZI] Specifically methylates the N(7) position of guanine 1405 in 16S rRNA. Confers resistance to various aminoglycosides, including gentamicin, kanamycin and sisomicin.<ref>PMID:1447159</ref> <ref>PMID:19589804</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lc/3lcu_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lc/3lcu_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Micromonospora zionensis marquez et al]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Husain, N]] | + | [[Category: Micromonospora zionensis]] |
| - | [[Category: Sivaraman, J]] | + | [[Category: Husain N]] |
| - | [[Category: Antibiotic resistance]] | + | [[Category: Sivaraman J]] |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
SGM_MICZI Specifically methylates the N(7) position of guanine 1405 in 16S rRNA. Confers resistance to various aminoglycosides, including gentamicin, kanamycin and sisomicin.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Sgm (Sisomicin-gentamicin methyltransferase) from antibiotic-producing bacterium Micromonospora zionensis is an enzyme that confers resistance to aminoglycosides like gentamicin and sisomicin by specifically methylating G1405 in bacterial 16S rRNA. Sgm belongs to the aminoglycoside resistance methyltransferase (Arm) family of enzymes that have been recently found to spread by horizontal gene transfer among disease-causing bacteria. Structural characterization of Arm enzymes is the key to understand their mechanism of action and to develop inhibitors that would block their activity. Here we report the structure of Sgm in complex with cofactors S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) at 2.0 and 2.1 A resolution, respectively, and results of mutagenesis and rRNA footprinting, and protein-substrate docking. We propose the mechanism of methylation of G1405 by Sgm and compare it with other m(7)G methyltransferases, revealing a surprising diversity of active sites and binding modes for the same basic reaction of RNA modification. This analysis can serve as a stepping stone towards developing drugs that would specifically block the activity of Arm methyltransferases and thereby re-sensitize pathogenic bacteria to aminoglycoside antibiotics.
Structural basis for the methylation of G1405 in 16S rRNA by aminoglycoside resistance methyltransferase Sgm from an antibiotic producer: a diversity of active sites in m7G methyltransferases.,Husain N, Tkaczuk KL, Tulsidas SR, Kaminska KH, Cubrilo S, Maravic-Vlahovicek G, Bujnicki JM, Sivaraman J Nucleic Acids Res. 2010 Jul 1;38(12):4120-32. Epub 2010 Mar 1. PMID:20194115[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kojic M, Topisirovic L, Vasiljevic B. Cloning and characterization of an aminoglycoside resistance determinant from Micromonospora zionensis. J Bacteriol. 1992 Dec;174(23):7868-72. PMID:1447159
- ↑ Savic M, Lovric J, Tomic TI, Vasiljevic B, Conn GL. Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics. Nucleic Acids Res. 2009 Sep;37(16):5420-31. doi: 10.1093/nar/gkp575. Epub 2009, Jul 9. PMID:19589804 doi:10.1093/nar/gkp575
- ↑ Husain N, Tkaczuk KL, Tulsidas SR, Kaminska KH, Cubrilo S, Maravic-Vlahovicek G, Bujnicki JM, Sivaraman J. Structural basis for the methylation of G1405 in 16S rRNA by aminoglycoside resistance methyltransferase Sgm from an antibiotic producer: a diversity of active sites in m7G methyltransferases. Nucleic Acids Res. 2010 Jul 1;38(12):4120-32. Epub 2010 Mar 1. PMID:20194115 doi:10.1093/nar/gkq122
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