6ifx: Difference between revisions
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==Crystal structure of chimeric KsgA with loop 12 from Erm== | |||
<StructureSection load='6ifx' size='340' side='right' caption='[[6ifx]], [[Resolution|resolution]] 3.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ifx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IFX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IFX FirstGlance]. <br> | |||
</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/16S_rRNA_(adenine(1518)-N(6)/adenine(1519)-N(6))-dimethyltransferase 16S rRNA (adenine(1518)-N(6)/adenine(1519)-N(6))-dimethyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.182 2.1.1.182] </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=6ifx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ifx OCA], [http://pdbe.org/6ifx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ifx RCSB], [http://www.ebi.ac.uk/pdbsum/6ifx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ifx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/RSMA_BACSU RSMA_BACSU]] Specifically dimethylates two adjacent adenosines (A1518 and A1519) in the loop of a conserved hairpin near the 3'-end of 16S rRNA in the 30S particle. May play a critical role in biogenesis of 30S subunits.[HAMAP-Rule:MF_00607] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Post-translational methylation of ribosomal RNA at select positions is a prevalent resistance mechanism adopted by pathogens. In this work, KsgA, a housekeeping ribosomal methyltransferase (rMtase) involved in ribosome biogenesis, was exploited as a model system to delineate the specific targeting determinants that impart substrate specificity to rMtases. With a combination of evolutionary and structure-guided approaches, a set of chimeras were created that altered the targeting specificity of KsgA such that it acted similarly to erythromycin-resistant methyltransferases (Erms), rMtases found in multidrug-resistant pathogens. The results revealed that specific loop embellishments on the basic Rossmann fold are key determinants in the selection of the cognate RNA. Moreover, in vivo studies confirmed that chimeric constructs are competent in imparting macrolide resistance. This work explores the factors that govern the emergence of resistance and paves the way for the design of specific inhibitors useful in reversing antibiotic resistance. | |||
Deciphering Determinants in Ribosomal Methyltransferases that Confer Antimicrobial Resistance.,Bhujbalrao R, Anand R J Am Chem Soc. 2019 Jan 9. doi: 10.1021/jacs.8b10277. PMID:30624914<ref>PMID:30624914</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ifx" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Anand, R]] | [[Category: Anand, R]] | ||
[[Category: Bhujbalrao, R]] | [[Category: Bhujbalrao, R]] | ||
[[Category: Chimera]] | |||
[[Category: Ksga]] | |||
[[Category: Resistance]] | |||
[[Category: Transferase]] | |||
Revision as of 12:53, 13 February 2019
Crystal structure of chimeric KsgA with loop 12 from ErmCrystal structure of chimeric KsgA with loop 12 from Erm
Structural highlights
Function[RSMA_BACSU] Specifically dimethylates two adjacent adenosines (A1518 and A1519) in the loop of a conserved hairpin near the 3'-end of 16S rRNA in the 30S particle. May play a critical role in biogenesis of 30S subunits.[HAMAP-Rule:MF_00607] Publication Abstract from PubMedPost-translational methylation of ribosomal RNA at select positions is a prevalent resistance mechanism adopted by pathogens. In this work, KsgA, a housekeeping ribosomal methyltransferase (rMtase) involved in ribosome biogenesis, was exploited as a model system to delineate the specific targeting determinants that impart substrate specificity to rMtases. With a combination of evolutionary and structure-guided approaches, a set of chimeras were created that altered the targeting specificity of KsgA such that it acted similarly to erythromycin-resistant methyltransferases (Erms), rMtases found in multidrug-resistant pathogens. The results revealed that specific loop embellishments on the basic Rossmann fold are key determinants in the selection of the cognate RNA. Moreover, in vivo studies confirmed that chimeric constructs are competent in imparting macrolide resistance. This work explores the factors that govern the emergence of resistance and paves the way for the design of specific inhibitors useful in reversing antibiotic resistance. Deciphering Determinants in Ribosomal Methyltransferases that Confer Antimicrobial Resistance.,Bhujbalrao R, Anand R J Am Chem Soc. 2019 Jan 9. doi: 10.1021/jacs.8b10277. PMID:30624914[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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