4ox9
From Proteopedia
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==Crystal structure of the aminoglycoside resistance methyltransferase NpmA bound to the 30S ribosomal subunit== | ==Crystal structure of the aminoglycoside resistance methyltransferase NpmA bound to the 30S ribosomal subunit== | ||
| - | <StructureSection load='4ox9' size='340' side='right' caption='[[4ox9]], [[Resolution|resolution]] 3.80Å' scene=''> | + | <StructureSection load='4ox9' size='340' side='right'caption='[[4ox9]], [[Resolution|resolution]] 3.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[4ox9]] is a | + | <table><tr><td colspan='2'>[[4ox9]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] and [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OX9 FirstGlance]. <br> |
| - | <b> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.8035Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SFG:SINEFUNGIN'>SFG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4ox9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ox9 OCA], [https://pdbe.org/4ox9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ox9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ox9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ox9 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RS4_THET8 RS4_THET8] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it helps nucleate assembly of the body and platform of the 30S subunit. Binds mRNA in the 70S ribosome, positioning it for translation.[HAMAP-Rule:MF_01306_B] | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Aminoglycosides are potent, broad spectrum, ribosome-targeting antibacterials whose clinical efficacy is seriously threatened by multiple resistance mechanisms. Here, we report the structural basis for 30S recognition by the novel plasmid-mediated aminoglycoside-resistance rRNA methyltransferase A (NpmA). These studies are supported by biochemical and functional assays that define the molecular features necessary for NpmA to catalyze m1A1408 modification and confer resistance. The requirement for the mature 30S as a substrate for NpmA is clearly explained by its recognition of four disparate 16S rRNA helices brought into proximity by 30S assembly. Our structure captures a "precatalytic state" in which multiple structural reorganizations orient functionally critical residues to flip A1408 from helix 44 and position it precisely in a remodeled active site for methylation. Our findings provide a new molecular framework for the activity of aminoglycoside-resistance rRNA methyltransferases that may serve as a functional paradigm for other modification enzymes acting late in 30S biogenesis. | Aminoglycosides are potent, broad spectrum, ribosome-targeting antibacterials whose clinical efficacy is seriously threatened by multiple resistance mechanisms. Here, we report the structural basis for 30S recognition by the novel plasmid-mediated aminoglycoside-resistance rRNA methyltransferase A (NpmA). These studies are supported by biochemical and functional assays that define the molecular features necessary for NpmA to catalyze m1A1408 modification and confer resistance. The requirement for the mature 30S as a substrate for NpmA is clearly explained by its recognition of four disparate 16S rRNA helices brought into proximity by 30S assembly. Our structure captures a "precatalytic state" in which multiple structural reorganizations orient functionally critical residues to flip A1408 from helix 44 and position it precisely in a remodeled active site for methylation. Our findings provide a new molecular framework for the activity of aminoglycoside-resistance rRNA methyltransferases that may serve as a functional paradigm for other modification enzymes acting late in 30S biogenesis. | ||
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Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA.,Dunkle JA, Vinal K, Desai PM, Zelinskaya N, Savic M, West DM, Conn GL, Dunham CM Proc Natl Acad Sci U S A. 2014 Apr 9. PMID:24717845<ref>PMID:24717845</ref> | Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA.,Dunkle JA, Vinal K, Desai PM, Zelinskaya N, Savic M, West DM, Conn GL, Dunham CM Proc Natl Acad Sci U S A. 2014 Apr 9. PMID:24717845<ref>PMID:24717845</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 4ox9" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Ribosomal protein THX 3D structures|Ribosomal protein THX 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
| - | [[Category: | + | [[Category: Thermus thermophilus HB8]] |
| - | [[Category: | + | [[Category: Conn GL]] |
| - | [[Category: | + | [[Category: Dunham CM]] |
| - | [[Category: | + | [[Category: Dunkle JA]] |
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Current revision
Crystal structure of the aminoglycoside resistance methyltransferase NpmA bound to the 30S ribosomal subunit
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