spacer
spacer

PDBsum entry 1qam

Go to PDB code: 
protein ligands links
Transferase PDB id
1qam
Jmol
Contents
Protein chain
235 a.a. *
Ligands
ACT ×2
Waters ×197
* Residue conservation analysis
PDB id:
1qam
Name: Transferase
Title: The structure of the rrna methyltransferase ermc': implications for the reaction mechanism
Structure: Ermc' methyltransferase. Chain: a. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.20Å     R-factor:   0.221     R-free:   0.251
Authors: G.Schluckebier,P.Zhong,K.D.Stewart,T.J.Kavanaugh,C.Abad- Zapatero
Key ref:
G.Schluckebier et al. (1999). The 2.2 A structure of the rRNA methyltransferase ErmC' and its complexes with cofactor and cofactor analogs: implications for the reaction mechanism. J Mol Biol, 289, 277-291. PubMed id: 10366505 DOI: 10.1006/jmbi.1999.2788
Date:
25-Mar-99     Release date:   29-Mar-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P13956  (ERM_BACIU) -  rRNA adenine N-6-methyltransferase
Seq:
Struc:
244 a.a.
235 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.1.1.184  - 23S rRNA (adenine(2085)-N(6))-dimethyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 S-adenosyl-L-methionine + adenine2085 in 23S rRNA = 2 S-adenosyl-L- homocysteine + N6-dimethyladenine2085 in 23S rRNA
2 × S-adenosyl-L-methionine
+ adenine(2085) in 23S rRNA
= 2 × S-adenosyl-L- homocysteine
+ N(6)-dimethyladenine(2085) in 23S rRNA
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to antibiotic   4 terms 
  Biochemical function     23S rRNA (adenine(2085)-N(6))-dimethyltransferase activity     6 terms  

 

 
    Added reference    
 
 
DOI no: 10.1006/jmbi.1999.2788 J Mol Biol 289:277-291 (1999)
PubMed id: 10366505  
 
 
The 2.2 A structure of the rRNA methyltransferase ErmC' and its complexes with cofactor and cofactor analogs: implications for the reaction mechanism.
G.Schluckebier, P.Zhong, K.D.Stewart, T.J.Kavanaugh, C.Abad-Zapatero.
 
  ABSTRACT  
 
The rRNA methyltransferase ErmC' transfers methyl groups from S -adenosyl-l-methionine to atom N6 of an adenine base within the peptidyltransferase loop of 23 S rRNA, thus conferring antibiotic resistance against a number of macrolide antibiotics. The crystal structures of ErmC' and of its complexes with the cofactor S -adenosyl-l-methionine, the reaction product S-adenosyl-l-homocysteine and the methyltransferase inhibitor Sinefungin, respectively, show that the enzyme undergoes small conformational changes upon ligand binding. Overall, the ligand molecules bind to the protein in a similar mode as observed for other methyltransferases. Small differences between the binding of the amino acid parts of the different ligands are correlated with differences in their chemical structure. A model for the transition-state based on the atomic details of the active site is consistent with a one-step methyl-transfer mechanism and might serve as a first step towards the design of potent Erm inhibitors.
 
  Selected figure(s)  
 
Figure 3.
Figure 4.
Figure 4. Comparison of the AdoMet conformation when bound to different AdoMet-dependent MTases: M. TaqI (blue, PDB entry 2ADM; [Schluckebier et al 1998]), catechol-O-MTase (red, 1VID; [Vidgren et al 1994]), RNA-O2′-MTase VP39 (green, 1VPT; [Hodel et al 1996]) and ErmC′ (this work). AdoMet was superimposed at the adenine rings. Prepared with QUANTA.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 289, 277-291) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20536733 H.Y.Kim, B.J.Kim, Y.Kook, Y.J.Yun, J.H.Shin, B.J.Kim, and Y.H.Kook (2010).
Mycobacterium massiliense is differentiated from Mycobacterium abscessus and Mycobacterium bolletii by erythromycin ribosome methyltransferase gene (erm) and clarithromycin susceptibility patterns.
  Microbiol Immunol, 54, 347-353.  
19697067 K.L.Tkaczuk (2010).
Trm13p, the tRNA:Xm4 modification enzyme from Saccharomyces cerevisiae is a member of the Rossmann-fold MTase superfamily: prediction of structure and active site.
  J Mol Model, 16, 599-606.  
20597089 S.J.Fleishman, J.E.Corn, E.M.Strauch, T.A.Whitehead, I.Andre, J.Thompson, J.J.Havranek, R.Das, P.Bradley, and D.Baker (2010).
Rosetta in CAPRI rounds 13-19.
  Proteins, 78, 3212-3218.  
19278652 C.Tu, J.E.Tropea, B.P.Austin, D.L.Court, D.S.Waugh, and X.Ji (2009).
Structural basis for binding of RNA and cofactor by a KsgA methyltransferase.
  Structure, 17, 374-385.
PDB codes: 3ftc 3ftd 3fte 3ftf
19285505 H.Demirci, R.Belardinelli, E.Seri, S.T.Gregory, C.Gualerzi, A.E.Dahlberg, and G.Jogl (2009).
Structural rearrangements in the active site of the Thermus thermophilus 16S rRNA methyltransferase KsgA in a binary complex with 5'-methylthioadenosine.
  J Mol Biol, 388, 271-282.
PDB codes: 3fut 3fuu 3fuv 3fuw 3fux
18959795 H.C.O'Farrell, Z.Xu, G.M.Culver, and J.P.Rife (2008).
Sequence and structural evolution of the KsgA/Dim1 methyltransferase family.
  BMC Res Notes, 1, 108.  
18844986 H.Grosjean, C.Gaspin, C.Marck, W.A.Decatur, and V.de Crécy-Lagard (2008).
RNomics and Modomics in the halophilic archaea Haloferax volcanii: identification of RNA modification genes.
  BMC Genomics, 9, 470.  
18038381 M.Feder, E.Purta, L.Koscinski, S.Cubrilo, G.Maravic Vlahovicek, and J.M.Bujnicki (2008).
Virtual screening and experimental verification to identify potential inhibitors of the ErmC methyltransferase responsible for bacterial resistance against macrolide antibiotics.
  ChemMedChem, 3, 316-322.  
17567576 H.Walbott, S.Auxilien, H.Grosjean, and B.Golinelli-Pimpaneau (2007).
The carboxyl-terminal extension of yeast tRNA m5C methyltransferase enhances the catalytic efficiency of the amino-terminal domain.
  J Biol Chem, 282, 23663-23671.  
17301155 J.Li, J.S.Chorba, and S.P.Whelan (2007).
Vesicular stomatitis viruses resistant to the methylase inhibitor sinefungin upregulate RNA synthesis and reveal mutations that affect mRNA cap methylation.
  J Virol, 81, 4104-4115.  
17932050 S.Zheng, S.Shuman, and B.Schwer (2007).
Sinefungin resistance of Saccharomyces cerevisiae arising from Sam3 mutations that inactivate the AdoMet transporter or from increased expression of AdoMet synthase plus mRNA cap guanine-N7 methyltransferase.
  Nucleic Acids Res, 35, 6895-6903.  
17868690 T.Christian, and Y.M.Hou (2007).
Distinct determinants of tRNA recognition by the TrmD and Trm5 methyl transferases.
  J Mol Biol, 373, 623-632.  
16971388 S.Zheng, S.Hausmann, Q.Liu, A.Ghosh, B.Schwer, C.D.Lima, and S.Shuman (2006).
Mutational analysis of Encephalitozoon cuniculi mRNA cap (guanine-N7) methyltransferase, structure of the enzyme bound to sinefungin, and evidence that cap methyltransferase is the target of sinefungin's antifungal activity.
  J Biol Chem, 281, 35904-35913.
PDB code: 2hv9
16768442 T.Christian, C.Evilia, and Y.M.Hou (2006).
Catalysis by the second class of tRNA(m1G37) methyl transferase requires a conserved proline.
  Biochemistry, 45, 7463-7473.  
16174779 C.T.Madsen, L.Jakobsen, K.Buriánková, F.Doucet-Populaire, J.L.Pernodet, and S.Douthwaite (2005).
Methyltransferase Erm(37) slips on rRNA to confer atypical resistance in Mycobacterium tuberculosis.
  J Biol Chem, 280, 38942-38947.  
16127056 C.T.Madsen, L.Jakobsen, and S.Douthwaite (2005).
Mycobacterium smegmatis Erm(38) is a reluctant dimethyltransferase.
  Antimicrob Agents Chemother, 49, 3803-3809.  
15929997 K.L.Constantine, S.R.Krystek, M.D.Healy, M.L.Doyle, N.O.Siemers, J.Thanassi, N.Yan, D.Xie, V.Goldfarb, J.Yanchunas, L.Tao, B.A.Dougherty, and B.T.Farmer (2005).
Structural and functional characterization of CFE88: evidence that a conserved and essential bacterial protein is a methyltransferase.
  Protein Sci, 14, 1472-1484.  
16245322 Y.G.Gao, M.Yao, Z.Yong, and I.Tanaka (2005).
Crystal structure of the putative RNA methyltransferase PH1948 from Pyrococcus horikoshii, in complex with the copurified S-adenosyl-L-homocysteine.
  Proteins, 61, 1141-1145.
PDB code: 1wy7
15749697 Y.Matsushima, C.Adán, R.Garesse, and L.S.Kaguni (2005).
Drosophila mitochondrial transcription factor B1 modulates mitochondrial translation but not transcription or DNA copy number in Schneider cells.
  J Biol Chem, 280, 16815-16820.  
15114858 G.Maravić, J.M.Bujnicki, and M.Flögel (2004).
Mutational analysis of basic residues in the N-terminus of the rRNA:m6A methyltransferase ErmC'.
  Folia Microbiol (Praha), 49, 3-7.  
14693532 K.Buriánková, F.Doucet-Populaire, O.Dorson, A.Gondran, J.C.Ghnassia, J.Weiser, and J.L.Pernodet (2004).
Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex.
  Antimicrob Agents Chemother, 48, 143-150.  
14999102 K.Das, T.Acton, Y.Chiang, L.Shih, E.Arnold, and G.T.Montelione (2004).
Crystal structure of RlmAI: implications for understanding the 23S rRNA G745/G748-methylation at the macrolide antibiotic-binding site.
  Proc Natl Acad Sci U S A, 101, 4041-4046.
PDB code: 1p91
12907737 G.Maravić, J.M.Bujnicki, M.Feder, S.Pongor, and M.Flögel (2003).
Alanine-scanning mutagenesis of the predicted rRNA-binding domain of ErmC' redefines the substrate-binding site and suggests a model for protein-RNA interactions.
  Nucleic Acids Res, 31, 4941-4949.  
12876362 H.C.O'Farrell, F.N.Musayev, J.N.Scarsdale, H.T.Wright, and J.P.Rife (2003).
Crystallization and preliminary X-ray diffraction analysis of KsgA, a universally conserved RNA adenine dimethyltransferase in Escherichia coli.
  Acta Crystallogr D Biol Crystallogr, 59, 1490-1492.  
12773376 H.J.Ahn, H.W.Kim, H.J.Yoon, B.I.Lee, S.W.Suh, and J.K.Yang (2003).
Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition.
  EMBO J, 22, 2593-2603.
PDB codes: 1uaj 1uak 1ual 1uam
12897151 V.McCulloch, and G.S.Shadel (2003).
Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity.
  Mol Cell Biol, 23, 5816-5824.  
11847284 C.D.Smith, M.Carson, A.M.Friedman, M.M.Skinner, L.Delucas, L.Chantalat, L.Weise, T.Shirasawa, and D.Chattopadhyay (2002).
Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-adenosyl homocysteine at 1.6-A resolution and modeling of an isoaspartyl-containing peptide at the active site.
  Protein Sci, 11, 625-635.
PDB code: 1i1n
12056895 G.D.Markham, P.O.Norrby, and C.W.Bock (2002).
S-adenosylmethionine conformations in solution and in protein complexes: conformational influences of the sulfonium group.
  Biochemistry, 41, 7636-7646.  
11929612 J.M.Bujnicki, and L.Rychlewski (2002).
RNA:(guanine-N2) methyltransferases RsmC/RsmD and their homologs revisited--bioinformatic analysis and prediction of the active site based on the uncharacterized Mj0882 protein structure.
  BMC Bioinformatics, 3, 10.  
11959553 K.A.Farrow, D.Lyras, G.Polekhina, K.Koutsis, M.W.Parker, and J.I.Rood (2002).
Identification of essential residues in the Erm(B) rRNA methyltransferase of Clostridium perfringens.
  Antimicrob Agents Chemother, 46, 1253-1261.  
11557810 X.Cheng, and R.J.Roberts (2001).
AdoMet-dependent methylation, DNA methyltransferases and base flipping.
  Nucleic Acids Res, 29, 3784-3795.  
11498400 P.Zhong, and V.D.Shortridge (2000).
The role of efflux in macrolide resistance.
  Drug Resist Updat, 3, 325-329.  
10858361 R.B.Giannattasio, and B.Weisblum (2000).
Modulation of erm methyltransferase activity by peptides derived from phage display.
  Antimicrob Agents Chemother, 44, 1961-1963.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.