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Methyltransferase
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PDB id
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2erc
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* Residue conservation analysis
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Enzyme class:
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E.C.2.1.1.184
- 23S rRNA (adenine(2085)-N(6))-dimethyltransferase.
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Reaction:
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2 S-adenosyl-L-methionine + adenine2085 in 23S rRNA = 2 S-adenosyl-L- homocysteine + N6-dimethyladenine2085 in 23S rRNA
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2
×
S-adenosyl-L-methionine
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+
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adenine(2085) in 23S rRNA
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=
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2
×
S-adenosyl-L- homocysteine
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+
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N(6)-dimethyladenine(2085) in 23S rRNA
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Biological process
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response to antibiotic
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2 terms
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Biochemical function
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transferase activity
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6 terms
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DOI no:
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Biochemistry
37:7103-7112
(1998)
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PubMed id:
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Crystal structure of ErmC', an rRNA methyltransferase which mediates antibiotic resistance in bacteria.
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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,
C.Abad-Zapatero.
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ABSTRACT
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The prevalent mechanism of bacterial resistance to erythromycin and other
antibiotics of the macrolide-lincosamide-streptogramin B group (MLS) is
methylation of the 23S rRNA component of the 50S subunit in bacterial ribosomes.
This sequence-specific methylation is catalyzed by the Erm group of
methyltransferases (MTases). They are found in several strains of pathogenic
bacteria, and ErmC is the most studied member of this class. The crystal
structure of ErmC' (a naturally occurring variant of ErmC) from Bacillus
subtilis has been determined at 3.0 A resolution by multiple anomalous
diffraction phasing methods. The structure consists of a conserved alpha/beta
amino-terminal domain which binds the cofactor S-adenosyl-l-methionine (SAM),
followed by a smaller, alpha-helical RNA-recognition domain. The beta-sheet
structure of the SAM-binding domain is well-conserved between the DNA, RNA, and
small-molecule MTases. However, the C-terminal nucleic acid binding domain
differs from the DNA-binding domains of other MTases and is unlike any
previously reported RNA-recognition fold. A large, positively charged, concave
surface is found at the interface of the N- and C-terminal domains and is
proposed to form part of the protein-RNA interaction surface. ErmC' exhibits the
conserved structural motifs previously found in the SAM-binding domain of other
methyltransferases. A model of SAM bound to ErmC' is presented which is
consistent with the motif conservation among MTases.
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Literature references that cite this PDB file's key reference
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| |
PubMed id
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Reference
|
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|
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.
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|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
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|
PDB codes:
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|
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.
|
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|
PDB codes:
|
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|
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.
|
|
|
|
|
|
|
M.Duo,
S.Hou,
and
D.Ren
(2008).
Identifying Escherichia coli genes involved in intrinsic multidrug resistance.
|
| |
Appl Microbiol Biotechnol, 81,
731-741.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
H.Yoneyama,
and
R.Katsumata
(2006).
Antibiotic resistance in bacteria and its future for novel antibiotic development.
|
| |
Biosci Biotechnol Biochem, 70,
1060-1075.
|
|
|
|
|
|
|
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.
|
|
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|
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|
|
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.
|
|
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|
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|
|
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:
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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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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:
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|
|
Y.Tanaka,
K.Tsumoto,
Y.Yasutake,
M.Umetsu,
M.Yao,
H.Fukada,
I.Tanaka,
and
I.Kumagai
(2004).
How oligomerization contributes to the thermostability of an archaeon protein. Protein L-isoaspartyl-O-methyltransferase from Sulfolobus tokodaii.
|
| |
J Biol Chem, 279,
32957-32967.
|
|
|
PDB code:
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|
|
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.
|
|
|
|
|
|
|
J.Kindrachuk,
J.Parent,
G.F.Davies,
M.Dinsmore,
S.Attah-Poku,
and
S.Napper
(2003).
Overexpression of L-isoaspartate O-methyltransferase in Escherichia coli increases heat shock survival by a mechanism independent of methyltransferase activity.
|
| |
J Biol Chem, 278,
50880-50886.
|
|
|
|
|
|
|
P.G.Foster,
C.R.Nunes,
P.Greene,
D.Moustakas,
and
R.M.Stroud
(2003).
The first structure of an RNA m5C methyltransferase, Fmu, provides insight into catalytic mechanism and specific binding of RNA substrate.
|
| |
Structure, 11,
1609-1620.
|
|
|
PDB codes:
|
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|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
K.S.McKeegan,
M.I.Borges-Walmsley,
and
A.R.Walmsley
(2002).
Microbial and viral drug resistance mechanisms.
|
| |
Trends Microbiol, 10,
S8-14.
|
|
|
|
|
|
|
M.P.Egloff,
D.Benarroch,
B.Selisko,
J.L.Romette,
and
B.Canard
(2002).
An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization.
|
| |
EMBO J, 21,
2757-2768.
|
|
|
PDB codes:
|
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|
|
|
|
|
O.Nureki,
M.Shirouzu,
K.Hashimoto,
R.Ishitani,
T.Terada,
M.Tamakoshi,
T.Oshima,
M.Chijimatsu,
K.Takio,
D.G.Vassylyev,
T.Shibata,
Y.Inoue,
S.Kuramitsu,
and
S.Yokoyama
(2002).
An enzyme with a deep trefoil knot for the active-site architecture.
|
| |
Acta Crystallogr D Biol Crystallogr, 58,
1129-1137.
|
|
|
PDB code:
|
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|
|
V.McCulloch,
B.L.Seidel-Rogol,
and
G.S.Shadel
(2002).
A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine.
|
| |
Mol Cell Biol, 22,
1116-1125.
|
|
|
|
|
|
|
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:
|
|
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|
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|
|
X.Cheng,
and
R.J.Roberts
(2001).
AdoMet-dependent methylation, DNA methyltransferases and base flipping.
|
| |
Nucleic Acids Res, 29,
3784-3795.
|
|
|
|
|
|
|
H.Bügl,
E.B.Fauman,
B.L.Staker,
F.Zheng,
S.R.Kushner,
M.A.Saper,
J.C.Bardwell,
and
U.Jakob
(2000).
RNA methylation under heat shock control.
|
| |
Mol Cell, 6,
349-360.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
H.Wang,
D.Boisvert,
K.K.Kim,
R.Kim,
and
S.H.Kim
(2000).
Crystal structure of a fibrillarin homologue from Methanococcus jannaschii, a hyperthermophile, at 1.6 A resolution.
|
| |
EMBO J, 19,
317-323.
|
|
|
PDB code:
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|
|
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:
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|
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|
|
R.B.Giannattasio,
and
B.Weisblum
(2000).
Modulation of erm methyltransferase activity by peptides derived from phage display.
|
| |
Antimicrob Agents Chemother, 44,
1961-1963.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
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.
|
|
|
|
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|
|
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.
|
|
|
|
|
|
|
Y.Hu,
J.Komoto,
Y.Huang,
T.Gomi,
H.Ogawa,
Y.Takata,
M.Fujioka,
and
F.Takusagawa
(1999).
Crystal structure of S-adenosylhomocysteine hydrolase from rat liver.
|
| |
Biochemistry, 38,
8323-8333.
|
|
|
PDB code:
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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.
|
|
|
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|
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.
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Links
