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S-Adenosyl-S-carboxymethyl-L-homocysteine: a novel cofactor found in the putative tRNA-modifying enzyme CmoA
- Source :
- Acta Crystallographica Section D: Biological Crystallography
- Publication Year :
- 2016
-
Abstract
- 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.<br />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.
- Subjects :
- putative tRNA-modification enzyme
Methyltransferase
Stereochemistry
Protein Data Bank (RCSB PDB)
macromolecular substances
010402 general chemistry
medicine.disease_cause
Crystallography, X-Ray
01 natural sciences
Cofactor
03 medical and health sciences
RNA, Transfer
Structural Biology
Tandem Mass Spectrometry
cmo5U biosynthesis
medicine
Escherichia coli
Transferase
030304 developmental biology
SCM-SAH
One-Carbon Group Transferases
chemistry.chemical_classification
0303 health sciences
biology
Escherichia coli Proteins
technology, industry, and agriculture
Active site
General Medicine
Research Papers
S-Adenosylhomocysteine
0104 chemical sciences
carbohydrates (lipids)
Enzyme
chemistry
Biochemistry
Transfer RNA
biology.protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Acta Crystallographica Section D: Biological Crystallography
- Accession number :
- edsair.doi.dedup.....4560b9701039d55928f5eeccb63fc82b