Insights into Catalysis by a Knotted TrmD tRNA Methyltransferase

Elkins, P.A.; Watts, Joseph; Zalacaı́n, Magdalena; Thiel, Adam van; Vitazka, Patrik; Redlak, Maria J.; Andraos-Selim, Cecile; Rastinejad, Fraydoon; Holmes, W M

doi:10.1016/j.jmb.2003.09.011

Cited by 115 publications

(220 citation statements)

References 31 publications

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“…While different in spatial configuration, each network is elaborate and comprehensive in the stabilization of the N 1 , N 6 , and N 7 of the adenine ring, the 29-and 39-OH of the ribose, and the carboxyl and amino groups of methionine in the methyl donor. These stabilizing forces are well visualized in a binary structure of TrmD with AdoMet and are preserved in a product complex with S-adenosyl homocysteine (AdoHcy) (Ahn et al 2003;Elkins et al 2003). They are also clearly identified in a binary structure of Trm5 with sinefungin and in a ternary structure with AdoMet and tRNA (Goto-Ito et al 2008).…”

Section: Introductionmentioning

confidence: 85%

“…While both enzymes recognize AdoMet as the methyl donor and G37-tRNA as the acceptor, they share no structural homology. TrmD functions as a homodimer and binds AdoMet using a rare trefoilknot fold (Ahn et al 2003;Elkins et al 2003), whereas Trm5 functions as a monomer and binds AdoMet using the popular protein fold known as the Rossmann fold (Goto-Ito et al 2008. Importantly, crystal structures of these enzymes show that the AdoMet structure when bound to TrmD exists in an L-shaped bent conformation (Ahn et al 2003), where the methionine moiety bends over the adenosine moiety, whereas the AdoMet structure when bound to Trm5 exists in an extended open conformation (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Differentiating analogous tRNA methyltransferases by fragments of the methyl donor

Lahoud¹,

Goto-Ito²,

Yoshida³

et al. 2011

RNA

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Bacterial TrmD and eukaryotic-archaeal Trm5 form a pair of analogous tRNA methyltransferase that catalyze methyl transfer from S-adenosyl methionine (AdoMet) to N 1 of G37, using catalytic motifs that share no sequence or structural homology. Here we show that natural and synthetic analogs of AdoMet are unable to distinguish TrmD from Trm5. Instead, fragments of AdoMet, adenosine and methionine, are selectively inhibitory of TrmD rather than Trm5. Detailed structural information of the two enzymes in complex with adenosine reveals how Trm5 escapes targeting by adopting an altered structure, whereas TrmD is trapped by targeting due to its rigid structure that stably accommodates the fragment. Free energy analysis exposes energetic disparities between the two enzymes in how they approach the binding of AdoMet versus fragments and provides insights into the design of inhibitors selective for TrmD.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Differentiating analogous tRNA methyltransferases by fragments of the methyl donor

Lahoud¹,

Goto-Ito²,

Yoshida³

et al. 2011

RNA

View full text Add to dashboard Cite

show abstract

“…41 In the case of m 1 G RNA methyltransferase (TrmD), 41 an aspartate residue was shown to be involved in the deprotonation step of N 1 of guanine. The two processes are likely to be different, as under physiological conditions, the N 1 of guanine is protonated but that of adenine is not.…”

Section: Superimposition Of T Thermophilus and M Tuberculosismentioning

confidence: 99%

Crystal Structure of Thermus thermophilus tRNA m1A58 Methyltransferase and Biophysical Characterization of Its Interaction with tRNA

Barraud

Golinelli‐Pimpaneau

Atmanène

et al. 2008

Journal of Molecular Biology

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“…5). Structurally equivalent arginine is also conserved in TrmD (R154 in E. coli) and is shown to be part of its catalytic center (Elkins et al 2003). The role of highly conserved arginine in the catalytic center of another SPOUT (Watanabe et al 2005).…”

Section: Ybea Protein Has C1915-specific Methyltransferase Activity Imentioning

confidence: 99%

Identification of pseudouridine methyltransferase in Escherichia coli

Ero¹,

Peil²,

Liiv³

et al. 2008

RNA

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In ribosomal RNA, modified nucleosides are found in functionally important regions, but their function is obscure. Stem-loop 69 of Escherichia coli 23S rRNA contains three modified nucleosides: pseudouridines at positions 1911 and 1917, and N3 methylpseudouridine (m 3 C) at position 1915. The gene for pseudouridine methyltransferase was previously not known. We identified E. coli protein YbeA as the methyltransferase methylating C1915 in 23S rRNA. The E. coli ybeA gene deletion strain lacks the N3 methylation at position 1915 of 23S rRNA as revealed by primer extension and nucleoside analysis by HPLC. Methylation at position 1915 is restored in the ybeA deletion strain when recombinant YbeA protein is expressed from a plasmid. In addition, we show that purified YbeA protein is able to methylate pseudouridine in vitro using 70S ribosomes but not 50S subunits from the ybeA deletion strain as substrate. Pseudouridine is the preferred substrate as revealed by the inability of YbeA to methylate uridine at position 1915. This shows that YbeA is acting at the final stage during ribosome assembly, probably during translation initiation. Hereby, we propose to rename the YbeA protein to RlmH according to uniform nomenclature of RNA methyltransferases. RlmH belongs to the SPOUT superfamily of methyltransferases. RlmH was found to be well conserved in bacteria, and the gene is present in plant and in several archaeal genomes. RlmH is the first pseudouridine specific methyltransferase identified so far and is likely to be the only one existing in bacteria, as m 3 C1915 is the only methylated pseudouridine in bacteria described to date.

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Insights into Catalysis by a Knotted TrmD tRNA Methyltransferase

Cited by 115 publications

References 31 publications

Differentiating analogous tRNA methyltransferases by fragments of the methyl donor

Differentiating analogous tRNA methyltransferases by fragments of the methyl donor

Crystal Structure of Thermus thermophilus tRNA m1A58 Methyltransferase and Biophysical Characterization of Its Interaction with tRNA

Identification of pseudouridine methyltransferase in Escherichia coli

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