Disease relevance of Tb10.6k15.3640

• Overproduction of highly active trypanosome alternative oxidase in Escherichia coli heme-deficient mutant [1].

High impact information on Tb10.6k15.3640

• In contrast, inhibition of the alternative oxidase, the second branch of the electron transport chain, with salicylhydroxamic acid overrides the effect of glucose or glycerol and causes a reduction in the level of GPEET mRNA [2].
• Site-directed mutagenesis reveals the essentiality of the conserved residues in the putative diiron active site of the trypanosome alternative oxidase [3].
• Attempts to knockout the trypanosome alternative oxidase genes (which are needed for glycerophosphate oxidase activity) were unsuccessful, but when we lowered the level of the corresponding mRNA by expressing a homologous double-stranded RNA, oxygen consumption was reduced fourfold and the rate of trypanosome growth was halved [4].
• We predicted that such properties would allow an inhibitor of the trypanosome alternative oxidase to be coadministered with glycerol as a means of providing treatment for infections by African trypanosomes [5].
• The mitochondrial electron transfer chain present in the procyclic form of the African trypanosome Trypanosoma brucei contains both cytochrome c oxidase and an alternative oxidase (TAO) as terminal oxidases that reduce oxygen to water [6].

Chemical compound and disease context of Tb10.6k15.3640

• Functional expression of the ascofuranone-sensitive Trypanosoma brucei brucei alternative oxidase in the cytoplasmic membrane of Escherichia coli [7].

Biological context of Tb10.6k15.3640

• Trypanosome alternative oxidase is regulated post-transcriptionally at the level of RNA stability [8].
• The causative agents, Trypanosoma brucei rhodesiense and T. b. gambiense, utilize a non-cytochrome, alternative oxidase (AOX) for their cellular respiration [9].
• Strain-specific difference in amino acid sequences of trypanosome alternative oxidase [10].

Anatomical context of Tb10.6k15.3640

• The trypanosome alternative oxidase exists as a monomer in Trypanosoma brucei mitochondria [11].

Associations of Tb10.6k15.3640 with chemical compounds

• Incubation of the parasites with the chelator leads to inhibition of DNA synthesis and lowers oxygen consumption indicating that deferoxamine may affect ribonucleotide reductase and alternative oxidase [12].
• The alternative oxidase inhibitor for Trypanosoma brucei, salicylhydroxamic acid (SHAM) had no effect on respiration while the cytochrome o inhibitor orthohydroxydiphenyl (OHD) could block cyanide-insensitive respiration at low concentrations [13].
• 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 [14].
• In long slender trypomastigotes the trypanosome alternative oxidase does not appear to be coupled to proton pumping, whereas in procyclic organisms the effects of inhibitors indicate that this oxidase may be coupled to a pathway that is branched preceding an antimycin A1-sensitive site [15].
• Molecular cloning and characterization of Trypanosoma vivax alternative oxidase (AOX) gene, a target of the trypanocide ascofuranone [16].

Other interactions of Tb10.6k15.3640

• This inhibition was suggested to be due to inhibition of the mitochondrial electron-transport system, composed of glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) and plant-like alternative oxidase [17].

Analytical, diagnostic and therapeutic context of Tb10.6k15.3640

• The trypanosome alternative oxidase (TAO) is an attractive target for chemotherapy for the diseases caused by African trypanosomes because there is no equivalent enzyme in mammalian hosts [18].

References