Literature summary for 1.10.3.11 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.

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Crystallization (Commentary)

Crystallization (Comment)	Organism
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

Crystallization (Comment)

Organism

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

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

Inhibitors

Inhibitors	Comment	Organism
5-chloro-3-[(2E)-3,7-dimethylocta-2,6-dienyl]-2,4-dihydroxy-6-methylbenzaldehyde	an ascofuranone derivative	Trypanosoma brucei
5-chloro-3-[(2E,6E)-8-hydroxy-3,7-dimethylnona-2,6-dienyl]-2,4-dihydroxy-6-methylbenzaldehyde	an ascofuranone derivative	Trypanosoma brucei
ascofuranone	an antibiotic	Trypanosoma brucei
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

Metals/Ions	Comment	Organism	Structure
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)

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

Organism

Organism	UniProt	Comment	Textmining
Trypanosoma brucei	Q26710	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2 ubiquinol + O2	-	Trypanosoma brucei	2 ubiquinone + 2 H2O	-	?
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

Subunits	Comment	Organism
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

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

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
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

General Information	Comment	Organism
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
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