Modomics - A Database of RNA Modifications

ID Card:

Full name: rRNA adenine N-1-methyltransferase
Synonym: aminoglycoside-resistance 16S rRNA methyltransferase
GI: 157734594
Orf: npmA
COG: COG0220
UniProt: A8C927
Structures: | 3P2E | 3P2I | 3P2K | 3PB3 | 3MTE | 4OX9 |
Alpha Fold Predicted Structure: AF-A8C927-F1
Enzyme type: methyltransferase
Position of modification - modification: s:1408(1408) - m1A


PDB Structures:


3P2E

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

X-ray crystal structures were determined of the broad-spectrum aminoglycoside-resistance A1408 16S rRNA methyltransferases KamB and NpmA, from the aminoglycoside-producer Streptoalloteichus tenebrarius and human pathogenic Escherichia coli, respectively. Consistent with their common function, both are Class I methyltransferases with additional highly conserved structural motifs that embellish the core SAM-binding fold. In overall structure, the A1408 rRNA methyltransferase were found to be most similar to a second family of Class I methyltransferases of distinct substrate specificity (m(7)G46 tRNA). Critical residues for A1408 rRNA methyltransferase activity were experimentally defined using protein mutagenesis and bacterial growth assays with kanamycin. Essential residues for SAM coenzyme binding and an extended protein surface that likely interacts with the 30S ribosomal subunit were thus revealed. The structures also suggest potential mechanisms of A1408 target nucleotide selection and positioning. We propose that a dynamic extended loop structure that is positioned adjacent to both the bound SAM and a functionally critical structural motif may mediate concerted conformational changes in rRNA and protein that underpin the specificity of target selection and activation of methyltransferase activity. These new structures provide important new insights that may provide a starting point for strategies to inhibit these emerging causes of pathogenic bacterial resistance to aminoglycosides.

Download RCSB-PDB Structures:

Pdb Files   3MTE.pdb   3P2E.pdb   3P2I.pdb   3P2K.pdb   3PB3.pdb   4OX9.pdb  
Pdbx/mmCIF Files   3MTE.cif   3P2E.cif   3P2I.cif   3P2K.cif   3PB3.cif   4OX9.cif  


Protein sequence:

MLILKGTKTVDLSKDELTEIIGQFDRVHIDLGTGDGRNIYKLAINDQNTFYIGIDPVKENLFDISKKIIKKPSKGGLSNVVFVIAAAESLPFELKNIADSISILFPWGTLLEYVIKPNRDILSNVADLAKKEAHFEFVTTYSDSYEEAEIKKRGLPLLSKAYFLSEQYKAELSNSGFRIDDVKELDNEYVKQFNSLWAKRLAFGRKRSFFRVSGHVSKH

Comments:

Only in pathogens (KamB family).




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
A:m1A RNA rRNA 1408 SSU-16S Prokaryotic Cytosol

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

M L I L K G T K T V D L S K D E L T E I I G Q F D R V H I D L G T G D G R N I Y K L A I N D Q N T F Y I G I D P V K E N L F D I S K K I I K K P S K G G L S N V V F V I A A A E S L P F E L K N I A D S I S I L F P W G T L L E Y V I K P N R D I L S N V A D L A K K E A H F E F V T T Y S D S Y E E A E I K K R G L P L L S K A Y F L S E Q Y K A E L S N S G F R I D D V K E L D N E Y V K Q F N S L W A K R L A F G R K R S F F R V S G H V S K H

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-A8C927-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-A8C927-F1.cif  
DSSP Secondary Structures   A8C927.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Wachino J, Shibayama K, Kurokawa H, Kimura K, Yamane K, Suzuki S, Shibata N, Ike Y, Arakawa Y Antimicrob Agents Chemother [details] 17875999 -
Structural insights into the function of aminoglycoside-resistance A1408 16S rRNA methyltransferases from antibiotic-producing and human pathogenic bacteria. Macmaster R, Zelinskaya N, Savic M, Rankin CR, Conn GL Nucleic Acids Res [details] 20639535 -
Structural basis for the methylation of A1408 in 16S rRNA by a panaminoglycoside resistance methyltransferase NpmA from a clinical isolate and analysis of the NpmA interactions with the 30S ribosomal subunit. Husain N, Obranic S, Koscinski L, Seetharaman J, Babic F, Bujnicki JM, Maravic-Vlahovicek G, Sivaraman J Nucleic Acids Res [details] 21062819 -
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 [details] 24717845 -