Crystal structure of CmoB bound with Cx-SAM in P21212
Classification:
TRANSFERASE
Technique:
X-Ray Diffraction
Resolution:
2.6
R value free:
0.256
R value observed:
0.223
R value work:
0.221
Abstract of the PDB Structure's related Publication:
Enzyme-mediated modifications at the wobble position of tRNAs are essential for the translation of the genetic code. We report the genetic, biochemical and structural characterization of CmoB, the enzyme that recognizes the unique metabolite carboxy-S-adenosine-L-methionine (Cx-SAM) and catalyzes a carboxymethyl transfer reaction resulting in formation of 5-oxyacetyluridine at the wobble position of tRNAs. CmoB is distinctive in that it is the only known member of the SAM-dependent methyltransferase (SDMT) superfamily that utilizes a naturally occurring SAM analog as the alkyl donor to fulfill a biologically meaningful function. Biochemical and genetic studies define the in vitro and in vivo selectivity for Cx-SAM as alkyl donor over the vastly more abundant SAM. Complementary high-resolution structures of the apo- and Cx-SAM bound CmoB reveal the determinants responsible for this remarkable discrimination. Together, these studies provide mechanistic insight into the enzymatic and non-enzymatic feature of this alkyl transfer reaction which affords the broadened specificity required for tRNAs to recognize multiple synonymous codons.
CmoB is an S-adenosyl-L-methionine dependent (SAM-dependent) methyltransferase belonging to the COG2230 ortholog gene family. It has been speculated its implication in a tRNA modification pathway where ho5U is modified to cmo5U (Kim et al. 2013 ).
Indeed, it has been observed to modify tRNAPro in a chain of reactions that implies the modification of U34 to ho5U34 by unidentified enzymes and hoU34 to mo5U by CmoB itself a the second step and the final modification of ho5U34 to cmoU34 by CmoA.(Nasvall et al. 2013 ).