The presence of four iron-containing superoxide dismutase isozymes in Trypanosomatidae : characterization, subcellular localization, and phylogenetic origin in Trypanosoma brucei
Edgcomb, Virginia P.
Opperdoes, Fred R.
MetadataShow full item record
KeywordAntioxidant enzymes; Evolution; Structural models; Subcellular localization; Superoxide dismutase; Trypanosoma
Metalloenzymes such as the superoxide dismutases (SODs) form part of a defense mechanism that helps protect obligate and facultative aerobic organisms from oxygen toxicity and damage. Here, we report the presence in the trypanosomatid genomes of four SOD genes: soda, sodb1 and sodb2 and a newly identified sodc. All four genes of Trypanosoma brucei have been cloned (Tbsods), sequenced and overexpressed in Escherichia coli and shown to encode active dimeric FeSOD isozymes. Homology modelling of the structures of all four enzymes using available X-ray crystal structures of homologs showed that the four TbSOD structures were nearly identical. Subcellular localization using GFP-fusion proteins in procyclic insect trypomastigotes shows that TbSODB1 is mainly cytosolic, with a minor glycosomal component, TbSODB2 is mainly glycosomal with some activity in the cytosol and TbSODA and TbSODC are both mitochondrial isozymes. Phylogenetic studies of all available trypanosomatid SODs and 106 dimeric FeSODs and closely related cambialistic dimeric SOD sequences suggest that the trypanosomatid SODs have all been acquired by more than one event of horizontal gene transfer, followed by events of gene duplication.
Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Free Radical Biology and Medicine 40 (2006): 210-225, doi:10.1016/j.freeradbiomed.2005.06.021.
Showing items related by title, author, creator and subject.
Sequence motif within trypanosome precursor tRNAs influences abundance and mitochondrial localization Sherrer, R. Lynn; Yermovsky-Kammerer, Audra E.; Hajduk, Stephen L. (American Society for Microbiology, 2003-12)Trypanosoma brucei lacks mitochondrial genes encoding tRNAs and must import nuclearly encoded tRNAs from the cytosol. The mechanism and specificity of this process remain unclear. We have identified a unique sequence motif, ...
Evaluation of pyrrolidine and pyrazolone derivatives as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1) Amata, Emanuele; Bland, Nicholas D.; Campbell, Robert K.; Pollastri, Michael P. (2015-04-13)Human African trypanosomiasis (HAT) is a parasitic disease, caused by the protozoan pathogen Trypanosoma brucei, which affects thousands every year and which is in need of new therapeutics. Herein we report the synthesis ...
Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs Ochiana, Stefan O.; Gustafson, Alden; Bland, Nicholas D.; Wang, Cuihua; Russo, Michael J.; Campbell, Robert K.; Pollastri, Michael P. (2012-02-02)In this report we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma ...