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

DOI: 10.1107/S0907444913004939 DOI Help
PMID: 23695253 PMID Help

Authors: Robert Byrne (University of York) , Fiona Whelan (University of York) , Pierre Aller (Diamond Light Source) , Louise Bird (Research Complex at Harwell) , Adam Dowle (University of York) , Carina Lobley (Diamond Light Source) , Yamini Reddivari (Research Complex at Harwell) , Joanne E. Nettleship (Research Complex at Harwell) , Ray Owens (University of Oxford) , Fred Antson (University of York) , David Waterman (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 69 , PAGES 1090 - 1098

State: Published (Approved)
Published: June 2013

Open Access Open Access

Abstract: Uridine at position 34 of bacterial transfer RNAs is commonly modified to uridine-5-oxyacetic acid (cmo5U) to increase the decoding capacity. The protein CmoA is involved in the formation of cmo5U 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.

Journal Keywords: Capacity; Crystal Structure; Crystallography; Crystals; Density; Electron Density; Electrons; Escherichia Coli; Interactions; Mass Spectroscopy; Modifications; Resolution; Salts

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Added On: 30/09/2013 15:12

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