Structural bioinformatics analysis of enzymes involved in the biosynthesis pathway of the hypermodified nucleoside ms2io6A37 in tRNA
Katarzyna H. Kaminska
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Search for more papers by this authorUrszula Baraniak
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Search for more papers by this authorMichal Boniecki
Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, PL-02-109 Warsaw, Poland
Search for more papers by this authorKatarzyna Nowaczyk
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Interdepartmental Laboratory of Molecular Biology, Institute of Plant Protection, Poznan, Poland
Search for more papers by this authorAnna Czerwoniec
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Search for more papers by this authorCorresponding Author
Janusz M. Bujnicki
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, PL-02-109 Warsaw, Poland
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Umultowska 89, PL-61-614 Poznan, Poland===Search for more papers by this authorKatarzyna H. Kaminska
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Search for more papers by this authorUrszula Baraniak
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Search for more papers by this authorMichal Boniecki
Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, PL-02-109 Warsaw, Poland
Search for more papers by this authorKatarzyna Nowaczyk
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Interdepartmental Laboratory of Molecular Biology, Institute of Plant Protection, Poznan, Poland
Search for more papers by this authorAnna Czerwoniec
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Search for more papers by this authorCorresponding Author
Janusz M. Bujnicki
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, PL-61-614 Poznan, Poland
Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, PL-02-109 Warsaw, Poland
Bioinformatics Laboratory, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Umultowska 89, PL-61-614 Poznan, Poland===Search for more papers by this authorAbstract
tRNAs from all organisms contain posttranscriptionally modified nucleosides, which are derived from the four canonical nucleosides. In most tRNAs that read codons beginning with U, adenosine in the position 37 adjacent to the 3′ position of the anticodon is modified to N6-(Δ2-isopentenyl) adenosine (i6A). In many bacteria, such as Escherichia coli, this residue is typically hypermodified to N6-isopentenyl-2-thiomethyladenosine (ms2i6A). In a few bacteria, such as Salmonella typhimurium, ms2i6A can be further hydroxylated to N6-(cis-4-hydroxyisopentenyl)-2-thiomethyladenosine (ms2io6A). Although the enzymes that introduce the respective modifications (prenyltransferase MiaA, methylthiotransferase MiaB, and hydroxylase MiaE) have been identified, their structures remain unknown and sequence-function relationships remain obscure. We carried out sequence analysis and structure prediction of MiaA, MiaB, and MiaE, using the protein fold-recognition approach. Three-dimensional models of all three proteins were then built using a new modeling protocol designed to overcome uncertainties in the alignments and divergence between the templates. For MiaA and MiaB, the catalytic core was built based on the templates from the P-loop NTPase and Radical-SAM superfamilies, respectively. For MiaB, we have also modeled the C-terminal TRAM domain and the newly predicted N-terminal flavodoxin-fold domain. For MiaE, we confidently predict that it shares the three-dimensional fold with the ferritin-like four-helix bundle proteins and that it has a similar active site and mechanism of action to diiron carboxylate enzymes, in particular, methane monooxygenase (E.C.1.14.13.25) that catalyses the biological hydroxylation of alkanes. Our models provide the first structural platform for enzymes involved in the biosynthesis of i6A, ms2i6A, and ms2io6A, explain the data available from the literature and will help to design further experiments and interpret their results. Proteins 2008. © 2007 Wiley-Liss, Inc.
Supporting Information
The Supplementary Material referred to in this article can be found online at http://www.interscience.wiley.com/jpages/0887-3585/suppmat/
| Filename | Description |
|---|---|
| EcMiaA.pdb165.6 KB | Supporting Information file EcMiaA.pdb |
| EcMiaB.pdb261.8 KB | Supporting Information file EcMiaB.pdb |
| StMiaE.pdb146.3 KB | Supporting Information file StMiaE.pdb |
| Figure4.models.revised.tif10.7 MB | Supporting Information file Figure4.models.revised.tif |
| MiaABESupplementaryfiguresandtables.pdf262 KB | Supporting Information file MiaABESupplementaryfiguresandtables.pdf |
| EcMiaA.pse6.5 MB | Supporting Information file EcMiaA.pse |
| EcMiaB.pse1.9 MB | Supporting Information file EcMiaB.pse |
| StMiaE.pse6.3 MB | Supporting Information file StMiaE.pse |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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