scholarly journals Targeting the Trypanosome Alternative Oxidase (TAO) as Promising Chemotherapeutic Approach for African Trypanosomiasis

2017 ◽  
Author(s):  
Christophe Dardonville ◽  
Francisco José Fueyo González ◽  
Carolina Izquierdo García ◽  
Teresa Díaz Ayuga ◽  
Godwin Ebiloma ◽  
...  
Keyword(s):  
Alternative Oxidase ◽  
African Trypanosomiasis ◽  
Chemotherapeutic Approach ◽  
Trypanosome Alternative Oxidase

scholarly journals African trypanosomiasis: Synthesis & SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase

2017 ◽  
Vol 141 ◽  
pp. 676-689 ◽  
Author(s):  
Ryan A. West ◽  
Oran G. O'Doherty ◽  
Trevor Askwith ◽  
John Atack ◽  
Paul Beswick ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Alternative Oxidase ◽  
African Trypanosomiasis ◽  
Trypanosome Alternative Oxidase ◽  
Novel Drug

Weak O2 binding and strong H2O2 binding at the non-heme diiron center of Trypanosome Alternative Oxidase

2020 ◽  
pp. 148356
Author(s):  
Sotaro Yamasaki ◽  
Mitsuo Shoji ◽  
Megumi Kayanuma ◽  
Vladimir Sladek ◽  
Daniel Ken Inaoka ◽  
...  
Keyword(s):  
Alternative Oxidase ◽  
Trypanosome Alternative Oxidase ◽  
O2 Binding

scholarly journals Crystallization and preliminary crystallographic analysis of trypanosome alternative oxidase

2008 ◽  
Vol 64 (a1) ◽  
pp. C275-C275
Author(s):  
Y. Kido ◽  
K. Sakamoto ◽  
D.K. Inaoka ◽  
S. Fujioka ◽  
T. Suzuki ◽  
...  
Keyword(s):  
Alternative Oxidase ◽  
Crystallographic Analysis ◽  
Trypanosome Alternative Oxidase

scholarly journals Trypanosome Alternative Oxidase Possesses both an N-Terminal and Internal Mitochondrial Targeting Signal

2014 ◽  
Vol 13 (4) ◽  
pp. 539-547 ◽  
Author(s):  
VaNae Hamilton ◽  
Ujjal K. Singha ◽  
Joseph T. Smith ◽  
Ebony Weems ◽  
Minu Chaudhuri
Keyword(s):  
Amino Acid ◽  
Alternative Oxidase ◽  
Heterologous Protein ◽  
Amino Acid Residues ◽  
Mitochondrial Targeting ◽  
Content Type ◽  
Targeting Signal ◽  
Internal Signal ◽  
Trypanosome Alternative Oxidase

ABSTRACTRecognition of mitochondrial targeting signals (MTS) by receptor translocases of outer and inner membranes of mitochondria is one of the prerequisites for import of nucleus-encoded proteins into this organelle. The MTS for a majority of trypanosomatid mitochondrial proteins have not been well defined. Here we analyzed the targeting signal for trypanosome alternative oxidase (TAO), which functions as the sole terminal oxidase in the infective form ofTrypanosoma brucei. Deleting the first 10 of 24 amino acids predicted to be the classical N-terminal MTS of TAO did not affect its import into mitochondriain vitro. Furthermore, ectopically expressed TAO was targeted to mitochondria in both forms of the parasite even after deletion of first 40 amino acid residues. However, deletion of more than 20 amino acid residues from the N terminus reduced the efficiency of import. These data suggest that besides an N-terminal MTS, TAO possesses an internal mitochondrial targeting signal. In addition, both the N-terminal MTS and the mature TAO protein were able to target a cytosolic protein, dihydrofolate reductase (DHFR), to aT. bruceimitochondrion. Further analysis identified a cryptic internal MTS of TAO, located within amino acid residues 115 to 146, which was fully capable of targeting DHFR to mitochondria. The internal signal was more efficient than the N-terminal MTS for import of this heterologous protein. Together, these results show that TAO possesses a cleavable N-terminal MTS as well as an internal MTS and that these signals act together for efficient import of TAO into mitochondria.

scholarly journals Purification of active recombinant trypanosome alternative oxidase

FEBS Letters ◽  
2003 ◽  
Vol 538 (1-3) ◽  
pp. 35-40 ◽  
Author(s):  
Coichi Nihei ◽  
Yoshihisa Fukai ◽  
Keisuke Kawai ◽  
Arihiro Osanai ◽  
Yoshisada Yabu ◽  
...  
Keyword(s):  
Alternative Oxidase ◽  
Trypanosome Alternative Oxidase

Purification of sn-glycerol-3-phosphate dehydrogenase from Trypanosoma brucei brucei

1992 ◽  
Vol 70 (2) ◽  
pp. 136-141 ◽  
Author(s):  
Jack A. Kornblatt ◽  
Joseph Nthale ◽  
Francis McOdimba
Keyword(s):  
Electron Transfer ◽  
Molecular Mass ◽  
Trypanosoma Brucei ◽  
Alternative Oxidase ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Trypanosoma Brucei Brucei ◽  
Subsequent Formation ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Trypanosome Alternative Oxidase

A protein has been purified from the membranes of bloodstream forms of Trypanosoma brucei brucei. The purified material contained a single polypeptide chain of molecular mass 67 kilodaltons as judged by sodium dodecyl sulfate –polyacrylamide gel electrophoresis; under "native" conditions it migrated through a Sephacryl S-300 column with a similar molecular mass. The purified protein catalysed electron transfer from sn-glycerol 3-phosphate to oxygen with the subsequent formation of water. Electron transfer by the purified enzyme to O2 was dependent on the presence of low concentrations of the mediator phenazine methosulfate. This protein is clearly the major membrane-bound sn-glycerol-3-phosphate dehydrogenase, but it also has some characteristics suggestive of the trypanosome alternative oxidase activities.Key words: trypanosomes, glycerophosphate dehydrogenase, trypanosome alternative oxidase.

The trypanosome alternative oxidase exists as a monomer in Trypanosoma brucei mitochondria

2005 ◽  
Vol 96 (3) ◽  
pp. 178-183 ◽  
Author(s):  
Minu Chaudhuri ◽  
Robert Daniel Ott ◽  
Lipi Saha ◽  
Shuntae Williams ◽  
George C. Hill
Keyword(s):  
Trypanosoma Brucei ◽  
Alternative Oxidase ◽  
Trypanosome Alternative Oxidase

scholarly journals Crystal Structure of the Trypanosomal Cyanide-Insensitive Alternative Oxidase in Complex with Drug Candidates for African Trypanosomiasis

2013 ◽  
Vol 55 (4) ◽  
pp. 254-259
Author(s):  
Tomoo SHIBA ◽  
Gen TAKAHASHI ◽  
Shigeharu HARADA ◽  
Hiroyuki SAIMOTO ◽  
Yasutoshi KIDO ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Alternative Oxidase ◽  
African Trypanosomiasis ◽  
Drug Candidates
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