Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification

Jungwook Kim, Hui Xiao, Junseock Koh, Yikai Wang, Jeffrey B. Bonanno, Keisha Thomas, Patricia C. Babbitt, Shoshana Brown, Young Sam Lee, Steven C. Almo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Enzyme-mediated modifications at the wobble position of tRNAs are essential for the translation of the genetic code. We report the genetic, biochemical and structural characterization of CmoB, the enzyme that recognizes the unique metabolite carboxy-S-adenosine-L-methionine (Cx-SAM) and catalyzes a carboxymethyl transfer reaction resulting in formation of 5-oxyacetyluridine at the wobble position of tRNAs. CmoB is distinctive in that it is the only known member of the SAM-dependent methyltransferase (SDMT) superfamily that utilizes a naturally occurring SAM analog as the alkyl donor to fulfill a biologically meaningful function. Biochemical and genetic studies define the in vitro and in vivo selectivity for Cx-SAM as alkyl donor over the vastly more abundant SAM. Complementary high-resolution structures of the apo- and Cx-SAM bound CmoB reveal the determinants responsible for this remarkable discrimination. Together, these studies provide mechanistic insight into the enzymatic and non-enzymatic feature of this alkyl transfer reaction which affords the broadened specificity required for tRNAs to recognize multiple synonymous codons.

Original languageEnglish (US)
Pages (from-to)4602-4613
Number of pages12
JournalNucleic Acids Research
Volume43
Issue number9
DOIs
StatePublished - Feb 27 2015

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Transferases
Transfer RNA
Methionine
Adenosine
Molecular Biology
Genetic Code
Methyltransferases
Enzymes
Codon

ASJC Scopus subject areas

  • Genetics

Cite this

Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification. / Kim, Jungwook; Xiao, Hui; Koh, Junseock; Wang, Yikai; Bonanno, Jeffrey B.; Thomas, Keisha; Babbitt, Patricia C.; Brown, Shoshana; Lee, Young Sam; Almo, Steven C.

In: Nucleic Acids Research, Vol. 43, No. 9, 27.02.2015, p. 4602-4613.

Research output: Contribution to journalArticle

Kim, J, Xiao, H, Koh, J, Wang, Y, Bonanno, JB, Thomas, K, Babbitt, PC, Brown, S, Lee, YS & Almo, SC 2015, 'Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification', Nucleic Acids Research, vol. 43, no. 9, pp. 4602-4613. https://doi.org/10.1093/nar/gkv206
Kim, Jungwook ; Xiao, Hui ; Koh, Junseock ; Wang, Yikai ; Bonanno, Jeffrey B. ; Thomas, Keisha ; Babbitt, Patricia C. ; Brown, Shoshana ; Lee, Young Sam ; Almo, Steven C. / Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification. In: Nucleic Acids Research. 2015 ; Vol. 43, No. 9. pp. 4602-4613.
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AU - Thomas, Keisha

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