Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA

  title={Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA},
  author={Heather C. Losey and Alexander J. Ruthenburg and Gregory L. Verdine},
  journal={Nature Structural \&Molecular Biology},
Bacterial tRNA adenosine deaminases (TadAs) catalyze the hydrolytic deamination of adenosine to inosine at the wobble position of tRNAArg2, a process that enables this single tRNA to recognize three different arginine codons in mRNA. In addition, inosine is also introduced at the wobble position of multiple eukaryotic tRNAs. The genes encoding these deaminases are essential in bacteria and yeast, demonstrating the importance of their biological activity. Here we report the crystallization and… 

The C-terminal end of the Trypanosoma brucei editing deaminase plays a critical role in tRNA binding.

It is shown that deletion of the last 10 amino acids at the C terminus of TbADAT2 abolishes tRNA binding, and the KR-domain provides a first glance at key residues involved in t RNA binding by eukaryotic tRNA editing deaminases.

Sequence-independent substrate selection by the eukaryotic wobble base deaminase ADAT2/3 involves multiple protein domains and distortion of the tRNA anticodon loop

The first structure of a eukaryotic ADAT2/3 deaminase bound to a full-length tRNA is presented, revealing that the enzyme distorts the anticodon loop, but in contrast to the bacterial enzymes, selects its substrate via sequence-independent contacts of eUKaryote-acquired flexible or intrinsically unfolded motifs distal from the conserved catalytic core.

Crystal structure of the yeast heterodimeric ADAT2/3 deaminase

A stepwise model for the pathway of deamination by ADAT2/3 is proposed, providing insight into the molecular mechanism of the A-to-I editing by the eukaryotic ADAT heterodimer, especially the role of ADAT3 in catalysis.

Structure of a tRNA-specific deaminase with compromised deamination activity.

This study provides structural insight into an alternative decoding and evolutionary strategy by a compromised TadA enzyme at a molecular level through structure-guided design through structural comparison between McTadA and other active TadA enzymes.

A Single Zinc Ion Is Sufficient for an Active Trypanosoma brucei tRNA Editing Deaminase*

It is shown by kinetic analyses and inductively coupled plasma emission spectrometry that wild type TbADAT2/3 coordinates two Zn2+ per heterodimer, but unlike any other tRNA deaminase, mutation of one of the key Zn 2+-coordinating cysteines in Tb ADAT2 yields a functional enzyme with a single-bound zinc.

Snapshots of dynamics in synthesizing N(6)-isopentenyladenosine at the tRNA anticodon.

The site-specific isopentenylation of RNA is ensured by a characteristic pinch-and-flip mechanism and by a reaction tunnel to confine the substrate selection.

Mechanisms of the tRNA wobble cytidine modification essential for AUA codon decoding in prokaryotes

  • T. Numata
  • Biology, Chemistry
    Bioscience, biotechnology, and biochemistry
  • 2015
In bacteria and archaea, the wobble cytidine of the AUA codon-specific tRNAIle is modified to 2-lysylcytidine and 2-agmatinylcyTidine by TilS and TiaS, respectively.

Molecular basis of cobalamin-dependent RNA modification

This work determined a series of high resolution structures of QueG from Bacillus subtilis and shows how this enzyme uses a HEAT-like domain to recognize the appropriate anticodons and position the hypermodified nucleoside into the enzyme active site, informing the understanding of Cbl dependent nucleic acid modification.

RNA editing in bacteria recodes multiple proteins and regulates an evolutionarily conserved toxin-antitoxin system.

This work focused on hokB, a toxin that confers antibiotic tolerance by growth inhibition, as it demonstrated the highest level of A-to-I RNA editing and identified the tRNA-specific adenosine deaminase (tadA) as the editing enzyme of all these editing sites, thus making it the first identified RNA editing enzyme that modifies both tRNAs and mRNAs.



tadA, an essential tRNA‐specific adenosine deaminase from Escherichia coli

It is shown that tadA is an essential gene in E.coli, underscoring the critical function of inosine at the wobble position in prokaryotes.

Crystal Structure of tRNA Adenosine Deaminase (TadA) from Aquifex aeolicus*

This study determined the crystal structure of Aquifex aeolicus TadA at a 1.8-Å resolution, the first structure of a deaminase acting on tRNA, and made a docking model of TadA with the tRNA anticodon stem loop.

Enzymatic conversion of adenosine to inosine and to N1-methylinosine in transfer RNAs: a review.

Tad1p, a yeast tRNA‐specific adenosine deaminase, is related to the mammalian pre‐mRNA editing enzymes ADAR1 and ADAR2

Tad1p has significant sequence similarity with the mammalian editing enzymes which act on specific precursor‐mRNAs and on long double‐stranded RNA, suggesting an evolutionary link between pre‐mRNA editing and tRNA modification.

Substrate analogues for an RNA-editing adenosine deaminase: mechanistic investigation and inhibitor design.

This and other results indicate that ADAR2 uses a base recognition strategy different from that of ADA, in contrast to adenosine deaminase (ADA), which catalyzes a similar reaction on nucleosides.

The uridine in "U-turn": contributions to tRNA-ribosomal binding.

The results demonstrate that proton donations by the N3-H and 2'OH groups of U33 are not absolutely required for ribosomal binding, and suggest that the overall uridine conformation, including a dynamic (C3'-endo > C2'-endo) sugar pucker, anti-conformation, and ability of uracil to stack between C32 and A35-phosphate, are the contributing factors to a functional U-turn.

Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations.

A stereoselective addition-elimination or SN2 mechanism of the enzyme is proposed with the zinc atom and the Glu and Asp residues playing key roles and a molecular explanation of a hereditary disease caused by several point mutations of an enzyme is presented.

RNA editing by adenosine deaminases that act on RNA.

  • B. Bass
  • Biology
    Annual review of biochemistry
  • 2002
This review summarizes ongoing investigations of the enzyme family and their substrates, focusing on biological function as well as biochemical mechanism.