6pqb

Crystal structure of aminoglycoside-resistance methyltransferase RmtC bound to S-adenosylhomocysteine (SAH)

spinqualitylabelsall models 6pqb, resolution 3.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6pqb is a 4 chain structure with sequence from Proteus mirabilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.14Å Ligands: SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RMTC_PROMI Specifically methylates the N(7) position of guanine 1405 in 16S rRNA. Confers resistance to various aminoglycosides, including gentamicin and kanamycin. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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