title: Structure of tRNA dimethylallyltransferase: RNA modification through a channel.
abstract: Dimethylallyltransferase (DMATase) transfers a five-carbon isoprenoid moiety from dimethylallyl pyrophosphate (DMAPP) to the amino group of adenosine at position 37 of certain tRNAs. Reported here are the crystal structures of Pseudomonas aeruginosa DMATase alone and in complex with pyrophosphate at 1.9 A resolution. Surprisingly, the enzyme possesses a central channel spanning the entire width of the enzyme. Both the accepting substrate tRNA and the donating substrate DMAPP appear to enter the channel from opposite sides in an ordered sequence, with tRNA first and DMAPP second, and the RNA modification reaction occurs in the middle of the channel once the two substrates have met. The structure of DMATase is homologous to a class of small soluble kinases involved in biosynthesis of nucleotide precursors for nucleic acids, indicating its possibly evolutionary origin. Furthermore, specific recognition of the pyrophosphate by a conserved loop in DMATase, similar to the P-loop commonly seen in diverse nucleotide-binding proteins, demonstrates that DMATase is structurally and mechanistically distinct from farnesyltransferase, another family of prenyltransferases involved in protein modification.
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Chun
authors.initials: C
authors.lastname: Zhou
authors.forename: Raven H
authors.initials: RH
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004122:Dimethylallyltranstransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000235:genetics; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D011994:Recombinant Proteins; D012343:RNA, Transfer; D004122:Dimethylallyltranstransferase