Modomics - A Database of RNA Modifications

ID Card:

Full name: rRNA adenine N-7-methyltransferase
Synonym: Sisomicin-gentamicin resistance methylase
GI: 75383291
Orf: sgm
COG: COG2263
UniProt: Q7M0R2
Structures: | 3LCU | 3LCV |
Alpha Fold Predicted Structure: AF-Q7M0R2-F1
Enzyme type: methyltransferase
Position of modification - modification: s:1405(1405) - m7G


PDB Structures:


3LCU

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Sgm (Sisomicin-gentamicin methyltransferase) from antibiotic-producing bacterium Micromonospora zionensis is an enzyme that confers resistance to aminoglycosides like gentamicin and sisomicin by specifically methylating G1405 in bacterial 16S rRNA. Sgm belongs to the aminoglycoside resistance methyltransferase (Arm) family of enzymes that have been recently found to spread by horizontal gene transfer among disease-causing bacteria. Structural characterization of Arm enzymes is the key to understand their mechanism of action and to develop inhibitors that would block their activity. Here we report the structure of Sgm in complex with cofactors S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) at 2.0 and 2.1 A resolution, respectively, and results of mutagenesis and rRNA footprinting, and protein-substrate docking. We propose the mechanism of methylation of G1405 by Sgm and compare it with other m(7)G methyltransferases, revealing a surprising diversity of active sites and binding modes for the same basic reaction of RNA modification. This analysis can serve as a stepping stone towards developing drugs that would specifically block the activity of Arm methyltransferases and thereby re-sensitize pathogenic bacteria to aminoglycoside antibiotics.

Download RCSB-PDB Structures:

Pdb Files   3LCU.pdb   3LCV.pdb  
Pdbx/mmCIF Files   3LCU.cif   3LCV.cif  


Protein sequence:

MTAPAADDRIDEIERAITKSRRYQTVAPATVRRLARAALVAARGDVPDAVKRTKRGLHEIYGAFLPPSPPNYAALLRHLDSAVDAGDDEAVRAALLRAMSVHISTRERLPHLDEFYRELFRHLPRPNTLRDLACGLNPLAAPWMGLPAETVYIASDIDARLVGFVDEALTRLNVPHRTNVADLLEDRLDEPADVTLLLKTLPCLETQQRGSGWEVIDIVNSPNIVVTFPTKSLGQRSKGMFQNYSQSFESQARERSCRIQRLEIGNELIYVIQK

Comments:

Methylation site was determined for E. coli rRNA.




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
G:m7G RNA rRNA 1405 LSU-23S Prokaryotic Cytosol 1447159   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-Q7M0R2-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q7M0R2-F1.cif  
DSSP Secondary Structures   Q7M0R2.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
Structural basis for the methylation of G1405 in 16S rRNA by aminoglycoside resistance methyltransferase Sgm from an antibiotic producer: a diversity of active sites in m7G methyltransferases. Husain N, Tkaczuk KL, Tulsidas SR, Kaminska KH, Cubrilo S, Maravic-Vlahovicek G, Bujnicki JM, Sivaraman J Nucleic Acids Res [details] 20194115 -
Cloning and characterization of an aminoglycoside resistance determinant from Micromonospora zionensis. Kojic M, Topisirovic L, Vasiljevic B J Bacteriol [details] 1447159 -
Critical residues for cofactor binding and catalytic activity in the aminoglycoside resistance methyltransferase Sgm. Savic M, Ilic-Tomic T, Macmaster R, Vasiljevic B, Conn GL J Bacteriol [details] 18586937 -