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1.  MODOMICS: a database of RNA modification pathways. 2008 update 
Nucleic Acids Research  2008;37(Database issue):D118-D121.
MODOMICS, a database devoted to the systems biology of RNA modification, has been subjected to substantial improvements. It provides comprehensive information on the chemical structure of modified nucleosides, pathways of their biosynthesis, sequences of RNAs containing these modifications and RNA-modifying enzymes. MODOMICS also provides cross-references to other databases and to literature. In addition to the previously available manually curated tRNA sequences from a few model organisms, we have now included additional tRNAs and rRNAs, and all RNAs with 3D structures in the Nucleic Acid Database, in which modified nucleosides are present. In total, 3460 modified bases in RNA sequences of different organisms have been annotated. New RNA-modifying enzymes have been also added. The current collection of enzymes includes mainly proteins for the model organisms Escherichia coli and Saccharomyces cerevisiae, and is currently being expanded to include proteins from other organisms, in particular Archaea and Homo sapiens. For enzymes with known structures, links are provided to the corresponding Protein Data Bank entries, while for many others homology models have been created. Many new options for database searching and querying have been included. MODOMICS can be accessed at
PMCID: PMC2686465  PMID: 18854352
2.  The architecture of the Schizosaccharomyces pombe CCR4-NOT complex 
Nature Communications  2016;7:10433.
CCR4-NOT is a large protein complex present both in cytoplasm and the nucleus of eukaryotic cells. Although it is involved in a variety of distinct processes related to expression of genetic information such as poly(A) tail shortening, transcription regulation, nuclear export and protein degradation, there is only fragmentary information available on some of its nine subunits. Here we show a comprehensive structural characterization of the native CCR4-NOT complex from Schizosaccharomyces pombe. Our cryo-EM 3D reconstruction of the complex, combined with techniques such as immunomicroscopy, RNA-nanogold labelling, docking of the available high-resolution structures and models of different subunits and domains, allow us to propose its full molecular architecture. We locate all functionally defined domains endowed with deadenylating and ubiquitinating activities, the nucleus-specific RNA-interacting subunit Mmi1, as well as surfaces responsible for protein–protein interactions. This information provides insight into cooperation of the different CCR4-NOT complex functions.
CCR4-NOT is a protein complex involved in a variety of important genetic processes. Here, the authors report the mid-resolution structure of this complex, and model the positions and contacts between the subunits, providing structural support for the previously reported functions of the complex.
PMCID: PMC4737751  PMID: 26804377
3.  Structural and functional insights into tRNA binding and adenosine N1-methylation by an archaeal Trm10 homologue 
Nucleic Acids Research  2015;44(2):940-953.
Purine nucleosides on position 9 of eukaryal and archaeal tRNAs are frequently modified in vivo by the post-transcriptional addition of a methyl group on their N1 atom. The methyltransferase Trm10 is responsible for this modification in both these domains of life. While certain Trm10 orthologues specifically methylate either guanosine or adenosine at position 9 of tRNA, others have a dual specificity. Until now structural information about this enzyme family was only available for the catalytic SPOUT domain of Trm10 proteins that show specificity toward guanosine. Here, we present the first crystal structure of a full length Trm10 orthologue specific for adenosine, revealing next to the catalytic SPOUT domain also N- and C-terminal domains. This structure hence provides crucial insights in the tRNA binding mechanism of this unique monomeric family of SPOUT methyltransferases. Moreover, structural comparison of this adenosine-specific Trm10 orthologue with guanosine-specific Trm10 orthologues suggests that the N1 methylation of adenosine relies on additional catalytic residues.
PMCID: PMC4737155  PMID: 26673726
4.  Structural and degradative aspects of ornithine decarboxylase antizyme inhibitor 2 
FEBS Open Bio  2014;4:510-521.
•AZIN2, unlike ornithine decarboxylase, exists as a monomer in solution.•Conserved residues among AZIN2 orthologs are critical for the binding to antizymes (AZs).•Substitution of the conserved residues affects the ability of AZIN2 to modulate polyamine levels.•AZIN2 and AZs are extremely labile proteins, which mutually stabilize each other.•Other proteolytic systems, besides the 26S proteasome, might be involved in AZIN2 degradation.
Ornithine decarboxylase (ODC) is the key enzyme in the polyamine biosynthetic pathway. ODC levels are controlled by polyamines through the induction of antizymes (AZs), small proteins that inhibit ODC and target it to proteasomal degradation without ubiquitination. Antizyme inhibitors (AZIN1 and AZIN2) are proteins homologous to ODC that bind to AZs and counteract their negative effect on ODC. Whereas ODC and AZIN1 are well-characterized proteins, little is known on the structure and stability of AZIN2, the lastly discovered member of this regulatory circuit. In this work we first analyzed structural aspects of AZIN2 by combining biochemical and computational approaches. We demonstrated that AZIN2, in contrast to ODC, does not form homodimers, although the predicted tertiary structure of the AZIN2 monomer was similar to that of ODC. Furthermore, we identified conserved residues in the antizyme-binding element, whose substitution drastically affected the capacity of AZIN2 to bind AZ1. On the other hand, we also found that AZIN2 is much more labile than ODC, but it is highly stabilized by its binding to AZs. Interestingly, the administration of the proteasome inhibitor MG132 caused differential effects on the three AZ-binding proteins, having no effect on ODC, preventing the degradation of AZIN1, but unexpectedly increasing the degradation of AZIN2. Inhibitors of the lysosomal function partially prevented the effect of MG132 on AZIN2. These results suggest that the degradation of AZIN2 could be also mediated by an alternative route to that of proteasome. These findings provide new relevant information on this unique regulatory mechanism of polyamine metabolism.
PMCID: PMC4066113  PMID: 24967154
AZ, antizyme; AZBE, antizyme-binding element; AZIN, antizyme inhibitor; ERGIC, endoplasmic reticulum-Golgi intermediate compartment; ODC, ornithine decarboxylase; GDT_TS, global distance test total score; HA, hemagglutinin; HEK, human embryonic kidney; PAGE, polyacrylamide gel electrophoresis; RMSD, root-mean-square deviation; TGN, trans-Golgi network; Antizyme; Antizyme-binding element; Homology modeling; Polyamines; Protein degradation; Proteasome inhibitors

Results 1-4 (4)