4IWN

Crystal structure of a putative methyltransferase CmoA in complex with a novel SAM derivative

Summary for 4IWN

• Entry DOI: 10.2210/pdb4iwn/pdb
• Descriptor: tRNA (cmo5U34)-methyltransferase, (2S)-4-[{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}(carboxylatomethyl)sulfonio] -2-ammoniobutanoate, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: putative trna modification enzyme, scm-sah, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 52585.73

Authors

Aller, P.,Lobley, C.M.,Byrne, R.T.,Antson, A.A.,Waterman, D.G. (deposition date: 2013-01-24, release date: 2013-05-29, Last modification date: 2023-09-20)

Primary citation

Byrne, R.T.,Whelan, F.,Aller, P.,Bird, L.E.,Dowle, A.,Lobley, C.M.,Reddivari, Y.,Nettleship, J.E.,Owens, R.J.,Antson, A.A.,Waterman, D.G.
S-Adenosyl-S-carboxymethyl-L-homocysteine: a novel cofactor found in the putative tRNA-modifying enzyme CmoA.
Acta Crystallogr.,Sect.D, 69:1090-1098, 2013

PubMed 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.

PubMed: 23695253
DOI: 10.1107/S0907444913004939

Experimental method

X-RAY DIFFRACTION (1.73 Å)