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Literature summary extracted from

  • Shiba, T.; Kido, Y.; Sakamoto, K.; Inaoka, D.K.; Tsuge, C.; Tatsumi, R.; Takahashi, G.; Balogun, E.O.; Nara, T.; Aoki, T.; Honma, T.; Tanaka, A.; Inoue, M.; Matsuoka, S.; Saimoto, H.; Moore, A.L.; Harada, S.; Kita, K.
    Structure of the trypanosome cyanide-insensitive alternative oxidase (2013), Proc. Natl. Acad. Sci. USA, 110, 4580-4585.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.10.3.11 trypanosomal alternative oxidase in the absence and presence of ascofuranone and ascofuranone derivative 5-chloro-3-[(2E,6E)-8-hydroxy-3,7-dimethylnona-2,6-dienyl]-2,4-dihydroxy-6-methylbenzaldehyde, the reservoir solution contains using 28-34% w/v PEG 400, 100 mM imidazole buffer (pH 7.4), and 500 mM potassium formate, X-ray diffraction structure determination and analysis, single-wavelength anomalous dispersion method, anomalous scattering effects caused by Fe measured to 3.2 A resolution Trypanosoma brucei

Protein Variants

EC Number Protein Variants Comment Organism
1.10.3.11 A216L site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 A216N site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 E213A site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 E215A site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 L122A site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 L122N site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 R118A site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 R118Q site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 T219V site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 Y220F site-directed mutagenesis, the mutation results in almost complete loss of ubiquinol oxidizing activity Trypanosoma brucei
1.10.3.11 Y246A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme Trypanosoma brucei

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.10.3.11 5-chloro-3-[(2E)-3,7-dimethylocta-2,6-dienyl]-2,4-dihydroxy-6-methylbenzaldehyde an ascofuranone derivative Trypanosoma brucei
1.10.3.11 5-chloro-3-[(2E,6E)-8-hydroxy-3,7-dimethylnona-2,6-dienyl]-2,4-dihydroxy-6-methylbenzaldehyde an ascofuranone derivative Trypanosoma brucei
1.10.3.11 ascofuranone an antibiotic Trypanosoma brucei
1.10.3.11 additional information inhibitor binding induces the ligation of a histidine residue in the active site, inhibitor binding site and structures, overview Trypanosoma brucei

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.10.3.11 Fe2+ the enzyme is a diiron carboxylate protein, the nonheme diiron carboxylate active site is buried within a four-helix bundle. The structure of the diiron active site was refined as an oxidized Fe(III)-Fe(III) form with a single hydroxo-bridge Trypanosoma brucei

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.10.3.11 2 ubiquinol + O2 Trypanosoma brucei
-
 2 ubiquinone + 2 H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.10.3.11 Trypanosoma brucei Q26710
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.10.3.11 2 ubiquinol + O2
-
 Trypanosoma brucei 2 ubiquinone + 2 H2O
-
 ?
1.10.3.11 2 ubiquinol + O2 ubiquinol binding model, overview. During the sequential electron reduction process, following the activation of oxygen, free radicals are generated on a tightly bound ubiquinol and Tyr220 Trypanosoma brucei 2 ubiquinone + 2 H2O
-
 ?

Subunits

EC Number Subunits Comment Organism
1.10.3.11 homodimer with two hydrophobic cavities per monomer. Both cavities bind ubiquinol and along with Tyr220 are required for the catalytic cycle for O2 reduction, but also inhibitors bind to one cavity and Tyr220, respectively. A second cavity interacts with the inhibitor-bindingcavity at the diiron center Trypanosoma brucei

Synonyms

EC Number Synonyms Comment Organism
1.10.3.11 AOX
-
 Trypanosoma brucei
1.10.3.11 cyanide-insensitive alternative oxidase
-
 Trypanosoma brucei
1.10.3.11 TAO
-
 Trypanosoma brucei
1.10.3.11 trypanosomal alternative oxidase
-
 Trypanosoma brucei

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.10.3.11 0.00000048
-
 pH and temperature not specified in the publication Trypanosoma brucei 5-chloro-3-[(2E,6E)-8-hydroxy-3,7-dimethylnona-2,6-dienyl]-2,4-dihydroxy-6-methylbenzaldehyde

General Information

EC Number General Information Comment Organism
1.10.3.11 additional information putative ubiquinol binding cavities, overview. The nonheme diiron carboxylate active site is buried within a four-helix bundle. The active site is ligated solely by four glutamate residues in its oxidized inhibitor-free state. Highly conserved Tyr220 iswithin 4 A of the active site and is critical for catalytic activity. The enzyme is a homodimer with two hydrophobic cavities per monomer. Both cavities bind ubiquinol and along with Tyr220 are required for the catalytic cycle for O2 reduction, but also inhibitors bind to one cavity and Tyr220, respectively. A second cavity interacts with the inhibitor-binding cavity at the diiron center. The active site, which is located in a hydrophobic environment deep inside the enzyme molecule, is composed of the diiron center and four glutamate (E123, E162, E213, and E266) and two histidine residues (H165 and H269), all of which are completely conserved Trypanosoma brucei
1.10.3.11 physiological function AOX is a diiron carboxylate protein that catalyzes the four-electron reduction of dioxygen to water by ubiquinol. AOX plays a critical role in the survival of the parasite in its bloodstream form Trypanosoma brucei