S-Adenosyl-S-carboxymethyl-l-homocysteine: a novel cofactor found in the putative tRNA-modifying enzyme CmoA
- University of York, Heslington YO10 5DD (United Kingdom)
- Diamond Light Source Ltd, Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)
- OPPF-UK, Research Complex at Harwell, R92 Rutherford Appleton Laboratory, Didcot, Oxfordshire OX11 0FA (United Kingdom)
The putative methyltransferase CmoA is involved in the nucleoside modification of transfer RNA. X-ray crystallography and mass spectrometry are used to show that it contains a novel SAM derivative, S-adenosyl-S-carboxymethyl-l-homocysteine, in which the donor methyl group is replaced by a carboxymethyl group. Uridine at position 34 of bacterial transfer RNAs is commonly modified to uridine-5-oxyacetic acid (cmo{sup 5}U) to increase the decoding capacity. The protein CmoA is involved in the formation of cmo{sup 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 http://scripts.iucr.org/cgi-bin/cr.cgi?rm, suggests that the active site contains SCM-SAH and not SAM.
- OSTI ID:
- 22347846
- Journal Information:
- Acta Crystallographica. Section D: Biological Crystallography, Vol. 69, Issue Pt 6; Other Information: PMCID: PMC3663124; PMID: 23695253; PUBLISHER-ID: be5227; OAI: oai:pubmedcentral.nih.gov:3663124; Copyright (c) Byrne et al. 2013; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0907-4449
- Country of Publication:
- Denmark
- Language:
- English
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