3A26

Crystal structure of P. horikoshii TYW2 in complex with MeSAdo

Summary for 3A26

• Entry DOI: 10.2210/pdb3a26/pdb
• Related: 3A25 3A27
• Descriptor: Uncharacterized protein PH0793, 5'-DEOXY-5'-METHYLTHIOADENOSINE, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: wybutosine modification, transferase
• Biological source: Pyrococcus horikoshii
• Cellular location: Cytoplasm (Potential): O58523
• Total number of polymer chains: 1
• Total formula weight: 35257.22

Authors

Umitsu, M.,Nishimasu, H.,Ishitani, R.,Nureki, O. (deposition date: 2009-04-28, release date: 2009-09-15, Last modification date: 2023-11-01)

Primary citation

Umitsu, M.,Nishimasu, H.,Noma, A.,Suzuki, T.,Ishitani, R.,Nureki, O.
Structural basis of AdoMet-dependent aminocarboxypropyl transfer reaction catalyzed by tRNA-wybutosine synthesizing enzyme, TYW2
Proc.Natl.Acad.Sci.USA, 106:15616-15621, 2009

PubMed Abstract: S-adenosylmethionine (AdoMet) is a methyl donor used by a wide variety of methyltransferases, and it is also used as the source of an alpha-amino-alpha-carboxypropyl ("acp") group by several enzymes. tRNA-yW synthesizing enzyme-2 (TYW2) is involved in the biogenesis of a hypermodified nucleotide, wybutosine (yW), and it catalyzes the transfer of the "acp" group from AdoMet to the C7 position of the imG-14 base, a yW precursor. This modified nucleoside yW is exclusively located at position 37 of eukaryotic tRNA(Phe), and it ensures the anticodon-codon pairing on the ribosomal decoding site. Although this "acp" group has a significant role in preventing decoding frame shifts, the mechanism of the "acp" group transfer by TYW2 remains unresolved. Here we report the crystal structures and functional analyses of two archaeal homologs of TYW2 from Pyrococcus horikoshii and Methanococcus jannaschii. The in vitro mass spectrometric and radioisotope-labeling analyses confirmed that these archaeal TYW2 homologues have the same activity as yeast TYW2. The crystal structures verified that the archaeal TYW2 contains a canonical class-I methyltransferase (MTase) fold. However, their AdoMet-bound structures revealed distinctive AdoMet-binding modes, in which the "acp" group, instead of the methyl group, of AdoMet is directed to the substrate binding pocket. Our findings, which were confirmed by extensive mutagenesis studies, explain why TYW2 transfers the "acp" group, and not the methyl group, from AdoMet to the nucleobase.

PubMed: 19717466
DOI: 10.1073/pnas.0905270106

Experimental method

X-RAY DIFFRACTION (2.5 Å)