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Acta Crystallogr D Biol Crystallogr. 2013 Jun;69(Pt 6):1090-8. doi: 10.1107/S0907444913004939. Epub 2013 May 15.

S-Adenosyl-S-carboxymethyl-L-homocysteine: a novel cofactor found in the putative tRNA-modifying enzyme CmoA.

Author information

1
York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington YO10 5DD, England.

Abstract

Uridine at position 34 of bacterial transfer RNAs is commonly modified to uridine-5-oxyacetic acid (cmo(5)U) to increase the decoding capacity. The protein CmoA is involved in the formation of cmo(5)U and was annotated as an S-adenosyl-L-methionine-dependent (SAM-dependent) methyltransferase on the basis of its sequence homology to other SAM-containing enzymes. However, both the crystal structure of Escherichia coli CmoA at 1.73 Å resolution and mass spectrometry demonstrate that it contains a novel cofactor, S-adenosyl-S-carboxymethyl-L-homocysteine (SCM-SAH), in which the donor methyl group is substituted by a carboxymethyl group. The carboxyl moiety forms a salt-bridge interaction with Arg199 that is conserved in a large group of CmoA-related proteins but is not conserved in other SAM-containing enzymes. This raises the possibility that a number of enzymes that have previously been annotated as SAM-dependent are in fact SCM-SAH-dependent. Indeed, inspection of electron density for one such enzyme with known X-ray structure, PDB entry 1im8, suggests that the active site contains SCM-SAH and not SAM.

KEYWORDS:

Escherichia coli; SCM-SAH; cmo5U biosynthesis; putative tRNA-modification enzyme

PMID:
23695253
PMCID:
PMC3663124
DOI:
10.1107/S0907444913004939
[Indexed for MEDLINE]
Free PMC Article
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