6pqb: Difference between revisions
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==Crystal structure of aminoglycoside-resistance methyltransferase RmtC bound to S-adenosylhomocysteine (SAH)== | |||
<StructureSection load='6pqb' size='340' side='right'caption='[[6pqb]], [[Resolution|resolution]] 3.14Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6pqb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Proteus_mirabilis Proteus mirabilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PQB FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.14Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=6pqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pqb OCA], [https://pdbe.org/6pqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pqb RCSB], [https://www.ebi.ac.uk/pdbsum/6pqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pqb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RMTC_PROMI RMTC_PROMI] Specifically methylates the N(7) position of guanine 1405 in 16S rRNA. Confers resistance to various aminoglycosides, including gentamicin and kanamycin.<ref>PMID:16377684</ref> <ref>PMID:20722735</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Methylation of the small ribosome subunit rRNA in the ribosomal decoding center results in exceptionally high-level aminoglycoside resistance in bacteria. Enzymes that methylate 16S rRNA on N7 of nucleotide G1405 (m7G1405) have been identified in both aminoglycoside-producing and clinically drug-resistant pathogenic bacteria. Using a fluorescence polarization 30S-binding assay and a new crystal structure of the methyltransferase RmtC at 3.14 A resolution, here we report a structure-guided functional study of 30S substrate recognition by the aminoglycoside resistance-associated 16S rRNA (m7G1405) methyltransferases. We found that the binding site for these enzymes in the 30S subunit directly overlaps with that of a second family of aminoglycoside resistance-associated 16S rRNA (m1A1408) methyltransferases, suggesting both groups of enzymes may exploit the same conserved rRNA tertiary surface for docking to the 30S. Within RmtC, we defined an N-terminal domain surface, comprising basic residues from both the N1 and N2 subdomains, that directly contributes to 30S-binding affinity. In contrast, additional residues lining a contiguous adjacent surface on the C-terminal domain were critical for 16S rRNA modification, but did not directly contribute to the binding affinity. The results from our experiments define the critical features of m7G1405 methyltransferase-substrate recognition and distinguish at least two distinct, functionally critical contributions of the tested enzyme residues: 30S-binding affinity and stabilizing a binding-induced 16S rRNA conformation necessary for G1405 modification. Our study sets the scene for future high-resolution structural studies of the 30S-methyltransferase complex and for potential exploitation of unique aspects of substrate recognition in future therapeutic strategies. | |||
Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition.,Nosrati M, Dey D, Mehrani A, Strassler SE, Zelinskaya N, Hoffer ED, Stagg SM, Dunham CM, Conn GL J Biol Chem. 2019 Oct 8. pii: RA119.011181. doi: 10.1074/jbc.RA119.011181. PMID:31594862<ref>PMID:31594862</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6pqb" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Proteus mirabilis]] | |||
[[Category: Conn GL]] | |||
[[Category: Hoffer ED]] | |||
[[Category: Nosrati M]] | |||
Latest revision as of 10:33, 11 October 2023
Crystal structure of aminoglycoside-resistance methyltransferase RmtC bound to S-adenosylhomocysteine (SAH)Crystal structure of aminoglycoside-resistance methyltransferase RmtC bound to S-adenosylhomocysteine (SAH)
Structural highlights
FunctionRMTC_PROMI Specifically methylates the N(7) position of guanine 1405 in 16S rRNA. Confers resistance to various aminoglycosides, including gentamicin and kanamycin.[1] [2] Publication Abstract from PubMedMethylation of the small ribosome subunit rRNA in the ribosomal decoding center results in exceptionally high-level aminoglycoside resistance in bacteria. Enzymes that methylate 16S rRNA on N7 of nucleotide G1405 (m7G1405) have been identified in both aminoglycoside-producing and clinically drug-resistant pathogenic bacteria. Using a fluorescence polarization 30S-binding assay and a new crystal structure of the methyltransferase RmtC at 3.14 A resolution, here we report a structure-guided functional study of 30S substrate recognition by the aminoglycoside resistance-associated 16S rRNA (m7G1405) methyltransferases. We found that the binding site for these enzymes in the 30S subunit directly overlaps with that of a second family of aminoglycoside resistance-associated 16S rRNA (m1A1408) methyltransferases, suggesting both groups of enzymes may exploit the same conserved rRNA tertiary surface for docking to the 30S. Within RmtC, we defined an N-terminal domain surface, comprising basic residues from both the N1 and N2 subdomains, that directly contributes to 30S-binding affinity. In contrast, additional residues lining a contiguous adjacent surface on the C-terminal domain were critical for 16S rRNA modification, but did not directly contribute to the binding affinity. The results from our experiments define the critical features of m7G1405 methyltransferase-substrate recognition and distinguish at least two distinct, functionally critical contributions of the tested enzyme residues: 30S-binding affinity and stabilizing a binding-induced 16S rRNA conformation necessary for G1405 modification. Our study sets the scene for future high-resolution structural studies of the 30S-methyltransferase complex and for potential exploitation of unique aspects of substrate recognition in future therapeutic strategies. Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition.,Nosrati M, Dey D, Mehrani A, Strassler SE, Zelinskaya N, Hoffer ED, Stagg SM, Dunham CM, Conn GL J Biol Chem. 2019 Oct 8. pii: RA119.011181. doi: 10.1074/jbc.RA119.011181. PMID:31594862[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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