Abstract:
:RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of Escherichia coli NudC in complex with substrate NAD and with cleavage product NMN reveal the catalytic residues lining the binding pocket and principles underlying molecular recognition of substrate and product. Biochemical mutation analysis identifies the conserved Nudix motif as the catalytic center of the enzyme, which needs to be homodimeric, as the catalytic pocket is composed of amino acids from both monomers. NudC is single-strand specific and has a purine preference for the 5'-terminal nucleotide. The enzyme strongly prefers NAD-linked RNA (NAD-RNA) over NAD and binds to a diverse set of cellular RNAs in an unspecific manner.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Höfer K,Li S,Abele F,Frindert J,Schlotthauer J,Grawenhoff J,Du J,Patel DJ,Jäschke Adoi
10.1038/nchembio.2132subject
Has Abstractpub_date
2016-09-01 00:00:00pages
730-4issue
9eissn
1552-4450issn
1552-4469pii
nchembio.2132journal_volume
12pub_type
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