Massive annotation of bacterial L-asparaginases reveals their puzzling distribution and frequent gene transfer events.

L-Asparaginases, which convert L-asparagine to L-aspartate and ammonia, come in five types, AI-AV. Some bacterial type AII enzymes are a key element in the treatment of acute lymphoblastic leukemia in children, but new L-asparaginases with better therapeutic properties are urgently needed. Here, we search publicly available bacterial genomes to annotate L-asparaginase proteins belonging to the five known types. We characterize taxonomic, phylogenetic, and genomic patterns of L-asparaginase occurrences pointing to frequent horizontal gene transfer (HGT) events, also occurring multiple times in the same recipient species. We show that the reference AV gene, encoding a protein originally found and structurally studied in Rhizobium etli, was acquired via HGT from Burkholderia. We also describe the sequence variability of the five L-asparaginase types and map the conservation levels on the experimental or predicted structures of the reference enzymes, finding the most conserved residues in the protein core near the active site, and the most variable ones on the protein surface. Additionally, we highlight the most common sequence features of bacterial AII proteins that may aid in selecting therapeutic L-asparaginases. Finally, we point to taxonomic units of bacteria that do not contain recognizable sequences of any of the known L-asparaginase types, implying that those microorganisms most likely contain new, as yet unknown types of L-asparaginases. Such novel enzymes, when properly identified and characterized, could hold promise as antileukemic drugs.

Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells.

Nicotine may affect cell function by rearranging protein complexes. We aimed to determine nicotine-induced alterations of protein complexes in Caenorhabditis elegans (C. elegans) cells, thereby revealing links between nicotine exposure and protein complex modulation. We compared the proteomic alterations induced by low and high nicotine concentrations (0.01 mM and 1 mM) with the control (no nicotine) in vivo by using mass spectrometry (MS)-based techniques, specifically the cetyltrimethylammonium bromide (CTAB) discontinuous gel electrophoresis coupled with liquid chromatography (LC)-MS/MS and spectral counting. As a result, we identified dozens of C. elegans proteins that are present exclusively or in higher abundance in either nicotine-treated or untreated worms. Based on these results, we report a possible network that captures the key protein components of nicotine-induced protein complexes and speculate how the different protein modules relate to their distinct physiological roles. Using functional annotation of detected proteins, we hypothesize that the identified complexes can modulate the energy metabolism and level of oxidative stress. These proteins can also be involved in modulation of gene expression and may be crucial in Alzheimer's disease. The findings reported in our study reveal putative intracellular interactions of many proteins with the cytoskeleton and may contribute to the understanding of the mechanisms of nicotinic acetylcholine receptor (nAChR) signaling and trafficking in cells.