PDBsum entry 1yub

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protein links
Methyltransferase PDB id
Protein chain
245 a.a. *
* Residue conservation analysis
PDB id:
Name: Methyltransferase
Title: Solution structure of an rrna methyltransferase (ermam) that confers macrolide-lincosamide-streptogramin antibiotic resistance, nmr, minimized average structure
Structure: Rrna methyltransferase. Chain: a. Synonym: ermam. Engineered: yes. Mutation: yes
Source: Streptococcus pneumoniae. Organism_taxid: 1313. Strain: 5728, a clinical isolate from abbott culture collection. Cell_line: bl21. Gene: erm. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 1 models
Authors: L.Yu,A.M.Petros,A.Schnuchel,P.Zhong,J.M.Severin,K.Walter, T.F.Holzman,S.W.Fesik
Key ref: L.Yu et al. (1997). Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance. Nat Struct Biol, 4, 483-489. PubMed id: 9187657
04-Mar-97     Release date:   04-Mar-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P21236  (ERM_STRPN) -  rRNA adenine N-6-methyltransferase
245 a.a.
245 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - 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    
Nat Struct Biol 4:483-489 (1997)
PubMed id: 9187657  
Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance.
L.Yu, A.M.Petros, A.Schnuchel, P.Zhong, J.M.Severin, K.Walter, T.F.Holzman, S.W.Fesik.
The Erm family of methyltransferases is responsible for the development of resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics. These enzymes methylate an adenine of 23S ribosomal RNA that prevents the MLS antibiotics from binding to the ribosome and exhibiting their antibacterial activity. Here we describe the three-dimensional structure of an Erm family member, ErmAM, as determined by NMR spectroscopy. The catalytic domain of ErmAM is structurally similar to that found in other methyltransferases and consists of a seven-stranded beta-sheet flanked by alpha-helices and a small two-stranded beta-sheet. In contrast to the catalytic domain, the substrate binding domain is different from other methyltransferases and adopts a novel fold that consists of four alpha-helices.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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
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.  
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.  
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.  
15637152 V.Tugarinov, W.Y.Choy, V.Y.Orekhov, and L.E.Kay (2005).
Solution NMR-derived global fold of a monomeric 82-kDa enzyme.
  Proc Natl Acad Sci U S A, 102, 622-627.
PDB code: 1y8b
16260766 W.Sun, X.Xu, M.Pavlova, A.M.Edwards, A.Joachimiak, A.Savchenko, and D.Christendat (2005).
The crystal structure of a novel SAM-dependent methyltransferase PH1915 from Pyrococcus horikoshii.
  Protein Sci, 14, 3121-3128.
PDB code: 2as0
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.  
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.  
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
15090247 J.E.Harlan, D.A.Egan, U.S.Ladror, S.Snyder, M.I.Tang, A.Buko, and T.F.Holzman (2003).
Driving affinity selection by centrifugal force.
  Assay Drug Dev Technol, 1, 507-519.  
12377117 G.Michel, V.Sauvé, R.Larocque, Y.Li, A.Matte, and M.Cygler (2002).
The structure of the RlmB 23S rRNA methyltransferase reveals a new methyltransferase fold with a unique knot.
  Structure, 10, 1303-1315.
PDB code: 1gz0
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.  
11567089 F.D.Schubot, C.J.Chen, J.P.Rose, T.A.Dailey, H.A.Dailey, and B.C.Wang (2001).
Crystal structure of the transcription factor sc-mtTFB offers insights into mitochondrial transcription.
  Protein Sci, 10, 1980-1988.
PDB code: 1i4w
11557810 X.Cheng, and R.J.Roberts (2001).
AdoMet-dependent methylation, DNA methyltransferases and base flipping.
  Nucleic Acids Res, 29, 3784-3795.  
11080641 M.M.Skinner, J.M.Puvathingal, R.L.Walter, and A.M.Friedman (2000).
Crystal structure of protein isoaspartyl methyltransferase: a catalyst for protein repair.
  Structure, 8, 1189-1201.
PDB code: 1dl5
11042458 N.K.Goto, and L.E.Kay (2000).
New developments in isotope labeling strategies for protein solution NMR spectroscopy.
  Curr Opin Struct Biol, 10, 585-592.  
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.  
10445878 A.K.Nielsen, S.Douthwaite, and B.Vester (1999).
Negative in vitro selection identifies the rRNA recognition motif for ErmE methyltransferase.
  RNA, 5, 1034-1041.  
9873020 A.Niewmierzycka, and S.Clarke (1999).
S-Adenosylmethionine-dependent methylation in Saccharomyces cerevisiae. Identification of a novel protein arginine methyltransferase.
  J Biol Chem, 274, 814-824.  
10329711 B.Holz, N.Dank, J.E.Eickhoff, G.Lipps, G.Krauss, and E.Weinhold (1999).
Identification of the binding site for the extrahelical target base in N6-adenine DNA methyltransferases by photo-cross-linking with duplex oligodeoxyribonucleotides containing 5-iodouracil at the target position.
  J Biol Chem, 274, 15066-15072.  
9931007 H.Pues, N.Bleimling, B.Holz, J.Wölcke, and E.Weinhold (1999).
Functional roles of the conserved aromatic amino acid residues at position 108 (motif IV) and position 196 (motif VIII) in base flipping and catalysis by the N6-adenine DNA methyltransferase from Thermus aquaticus.
  Biochemistry, 38, 1426-1434.  
9917069 L.H.Hansen, B.Vester, and S.Douthwaite (1999).
Core sequence in the RNA motif recognized by the ErmE methyltransferase revealed by relaxing the fidelity of the enzyme for its target.
  RNA, 5, 93.  
10454610 R.Reid, P.J.Greene, and D.V.Santi (1999).
Exposition of a family of RNA m(5)C methyltransferases from searching genomic and proteomic sequences.
  Nucleic Acids Res, 27, 3138-3145.  
9804844 A.M.Reeve, S.D.Breazeale, and C.A.Townsend (1998).
Purification, characterization, and cloning of an S-adenosylmethionine-dependent 3-amino-3-carboxypropyltransferase in nocardicin biosynthesis.
  J Biol Chem, 273, 30695-30703.  
  9628328 C.Schmutte, and P.A.Jones (1998).
Involvement of DNA methylation in human carcinogenesis.
  Biol Chem, 379, 377-388.  
9585521 D.E.Bussiere, S.W.Muchmore, C.G.Dealwis, G.Schluckebier, V.L.Nienaber, R.P.Edalji, K.A.Walter, U.S.Ladror, T.F.Holzman, and C.Abad-Zapatero (1998).
Crystal structure of ErmC', an rRNA methyltransferase which mediates antibiotic resistance in bacteria.
  Biochemistry, 37, 7103-7112.
PDB code: 2erc
9818180 G.M.Clore, and A.M.Gronenborn (1998).
NMR structure determination of proteins and protein complexes larger than 20 kDa.
  Curr Opin Chem Biol, 2, 564-570.  
9646872 K.H.Gardner, and L.E.Kay (1998).
The use of 2H, 13C, 15N multidimensional NMR to study the structure and dynamics of proteins.
  Annu Rev Biophys Biomol Struct, 27, 357-406.  
9862809 P.H.Tran, Z.R.Korszun, S.Cerritelli, S.S.Springhorn, and S.A.Lacks (1998).
Crystal structure of the DpnM DNA adenine methyltransferase from the DpnII restriction system of streptococcus pneumoniae bound to S-adenosylmethionine.
  Structure, 6, 1563-1575.
PDB code: 2dpm
9345633 L.E.Kay, and K.H.Gardner (1997).
Solution NMR spectroscopy beyond 25 kDa.
  Curr Opin Struct Biol, 7, 722-731.  
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.