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12  structures 583  species 0  interactions 1058  sequences 15  architectures

Family: AOX (PF01786)

Summary: Alternative oxidase

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This is the Wikipedia entry entitled "Alternative oxidase". More...

Alternative oxidase Edit Wikipedia article

Symbol AOX
Pfam PF01786
InterPro IPR002680
OPM superfamily 471
OPM protein 3w54
The alternative oxidase shown as part of the complete electron transport chain. UQ is ubiquinol/ubiquinone, C is cytochrome c and AOX is the alternative oxidase.

The alternative oxidase (AOX) is an enzyme that forms part of the electron transport chain in mitochondria of different organisms [1][2] Proteins homologous to the mitochondrial oxidase have also been identified in bacterial genomes.[3][4]

The oxidase provides an alternative route for electrons passing through the electron transport chain to reduce oxygen. However, as several proton-pumping steps are bypassed in this alternative pathway, activation of the oxidase reduces ATP generation. This enzyme was first identified as a distinct oxidase pathway from cytochrome c oxidase as the alternative oxidase is resistant to inhibition by the poison cyanide.[5]


The fungicide azoxystrobin.

This metabolic pathway leading to the alternative oxidase diverges from the cytochrome-linked electron transport chain at the ubiquinone pool.[6] Alternative pathway respiration only produces proton translocation at Complex 1 (NADH dehydrogenase) and so has a lower ATP yield than the full pathway. The expression of the alternative oxidase gene AOX is influenced by stresses such as cold, reactive oxygen species and infection by pathogens, as well as other factors that reduce electron flow through the cytochrome pathway of respiration.[7][8] Although the benefit conferred by this activity remains uncertain, it may enhance an organisms' ability to resist these stresses, through reducing the level of oxidative stress.[9]

Unusually, the bloodstream form of the protozoan parasite Trypanosoma brucei, which is the cause of sleeping sickness, depends entirely on the alternative oxidase pathway for cellular respiration through its electron transport chain.[10][11] This major metabolic difference between the parasite and its human host has made the T. brucei alternative oxidase an attractive target for drug design.[12][13] Of the known inhibitors of alternative oxidases, the antibiotic ascofuranone inhibits the T. brucei enzyme and cures infection in mice.[14][15]

In fungi, the ability of the alternative oxidase to bypass inhibition of parts of the electron transport chain can contribute to fungicide resistance. This is seen in the strobilurin fungicides that target complex III, such as azoxystrobin, picoxystrobin and fluoxastrobin.[16] However, as the alternative pathway generates less ATP, these fungicides are still effective in preventing spore germination, as this is an energy-intensive process.[17]

Structure and mechanism

The alternative oxidase is an integral monotopic membrane protein that is tightly bound to the inner mitochondrial membrane from matrix side[18] The enzyme has been predicted to contain a coupled diiron center on the basis of a conserved sequence motif consisting of the proposed iron ligands, four glutamate and two histidine amino acid residues.[19] The electron spin resonance study of Arabidopsis thaliana alternative oxidase AOX1a showed that the enzyme contains a hydroxo-bridged mixed-valent Fe(II)/Fe(III) binuclear iron center.[20] A catalytic cycle has been proposed that involves this di-iron center and at least one transient protein-derived free radical, which is probably formed on a tyrosine residue.[21]

See also


  1. ^ McDonald A, Vanlerberghe G (2004). "Branched mitochondrial electron transport in the Animalia: presence of alternative oxidase in several animal phyla". IUBMB Life 56 (6): 333–41. doi:10.1080/1521-6540400000876. PMID 15370881. 
  2. ^ Sluse FE, Jarmuszkiewicz W (1998). "Alternative oxidase in the branched mitochondrial respiratory network: an overview on structure, function, regulation, and role". Braz. J. Med. Biol. Res. 31 (6): 733–47. doi:10.1590/S0100-879X1998000600003. PMID 9698817. 
  3. ^ McDonald AE, Amirsadeghi S, Vanlerberghe GC (2003). "Prokaryotic orthologues of mitochondrial alternative oxidase and plastid terminal oxidase". Plant Mol. Biol. 53 (6): 865–76. doi:10.1023/B:PLAN.0000023669.79465.d2. PMID 15082931. 
  4. ^ Atteia A, van Lis R, van Hellemond JJ, Tielens AG, Martin W, Henze K (2004). "Identification of prokaryotic homologues indicates an endosymbiotic origin for the alternative oxidases of mitochondria (AOX) and chloroplasts (PTOX)". Gene 330: 143–8. doi:10.1016/j.gene.2004.01.015. PMID 15087133. 
  5. ^ Moore AL, Siedow JN (1991). "The regulation and nature of the cyanide-resistant alternative oxidase of plant mitochondria". Biochim. Biophys. Acta 1059 (2): 121–40. doi:10.1016/S0005-2728(05)80197-5. PMID 1883834. 
  6. ^ Juszczuk IM, Rychter AM (2003). "Alternative oxidase in higher plants" (PDF). Acta Biochim. Pol. 50 (4): 1257–71. PMID 14740012. 
  7. ^ Vanlerberghe GC, McIntosh L (1997). "Alternative oxidase: From Gene to Function". Annual Review of Plant Physiology and Plant Molecular Biology 48: 703–734. doi:10.1146/annurev.arplant.48.1.703. PMID 15012279. 
  8. ^ Ito Y, Saisho D, Nakazono M, Tsutsumi N, Hirai A (1997). "Transcript levels of tandem-arranged alternative oxidase genes in rice are increased by low temperature". Gene 203 (2): 121–9. doi:10.1016/S0378-1119(97)00502-7. PMID 9426242. 
  9. ^ Maxwell DP, Wang Y, McIntosh L (1999). "The alternative oxidase lowers mitochondrial reactive oxygen production in plant cells". Proc. Natl. Acad. Sci. U.S.A. 96 (14): 8271–6. doi:10.1073/pnas.96.14.8271. PMC 22224. PMID 10393984. 
  10. ^ Chaudhuri M, Ott RD, Hill GC (2006). "Trypanosome alternative oxidase: from molecule to function". Trends Parasitol. 22 (10): 484–91. doi:10.1016/ PMID 16920028. 
  11. ^ Clarkson AB, Bienen EJ, Pollakis G, Grady RW (1989). "Respiration of bloodstream forms of the parasite Trypanosoma brucei brucei is dependent on a plant-like alternative oxidase" (PDF). J. Biol. Chem. 264 (30): 17770–6. PMID 2808350. 
  12. ^ Nihei C, Fukai Y, Kita K (2002). "Trypanosome alternative oxidase as a target of chemotherapy". Biochim. Biophys. Acta 1587 (2-3): 234–9. doi:10.1016/s0925-4439(02)00086-8. PMID 12084465. 
  13. ^ Grady RW, Bienen EJ, Dieck HA, Saric M, Clarkson AB (1993). "N-n-alkyl-3,4-dihydroxybenzamides as inhibitors of the trypanosome alternative oxidase: activity in vitro and in vivo" (PDF). Antimicrob. Agents Chemother. 37 (5): 1082–5. doi:10.1128/aac.37.5.1082. PMC 187903. PMID 8517695. 
  14. ^ Minagawa N, Yabu Y, Kita K, Nagai K, Ohta N, Meguro K, Sakajo S, Yoshimoto A (1997). "An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei". Mol. Biochem. Parasitol. 84 (2): 271–80. doi:10.1016/S0166-6851(96)02797-1. PMID 9084049. 
  15. ^ Yabu Y, Yoshida A, Suzuki T, Nihei C, Kawai K, Minagawa N, Hosokawa T, Nagai K, Kita K, Ohta N (2003). "The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei brucei in mice". Parasitol. Int. 52 (2): 155–64. doi:10.1016/S1383-5769(03)00012-6. PMID 12798927. 
  16. ^ Miguez M, Reeve C, Wood PM, Hollomon DW (2004). "Alternative oxidase reduces the sensitivity of Mycosphaerella graminicola to QOI fungicides". Pest Manag. Sci. 60 (1): 3–7. doi:10.1002/ps.837. PMID 14727735. 
  17. ^ Avila-Adame C, Köller W (2003). "Impact of alternative respiration and target-site mutations on responses of germinating conidia of Magnaporthe grisea to Qo-inhibiting fungicides". Pest Manag. Sci. 59 (3): 303–9. doi:10.1002/ps.638. PMID 12639047. 
  18. ^ Berthold DA, Stenmark P (2003). "Membrane-bound diiron carboxylate proteins". Annual review of plant biology 54: 497–517. doi:10.1146/annurev.arplant.54.031902.134915. PMID 14503001. 
  19. ^ Berthold DA, Andersson ME, Nordlund P (2000). "New insight into the structure and function of the alternative oxidase". Biochim. Biophys. Acta 1460 (2-3): 241–54. doi:10.1016/S0005-2728(00)00149-3. PMID 11106766. 
  20. ^ Berthold DA, Voevodskaya N, Stenmark P, Gräslund A, Nordlund P (2002). "EPR studies of the mitochondrial alternative oxidase. Evidence for a diiron carboxylate center". J. Biol. Chem. 277 (46): 43608–14. doi:10.1074/jbc.M206724200. PMID 12215444. 
  21. ^ Affourtit C, Albury MS, Crichton PG, Moore AL (2002). "Exploring the molecular nature of alternative oxidase regulation and catalysis". FEBS Lett. 510 (3): 121–6. doi:10.1016/S0014-5793(01)03261-6. PMID 11801238. 

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Alternative oxidase Provide feedback

The alternative oxidase is used as a second terminal oxidase in the mitochondria, electrons are transfered directly from reduced ubiquinol to oxygen forming water [2]. This is not coupled to ATP synthesis and is not inhibited by cyanide, this pathway is a single step process [1]. In rice the transcript levels of the alternative oxidase are increased by low temperature [1].

Literature references

  1. Ito Y, Saisho D, Nakazono M, Tsutsumi N, Hirai A; , Gene 1997;203:121-129.: Transcript levels of tandem-arranged alternative oxidase genes in rice are increased by low temperature. PUBMED:9426242 EPMC:9426242

  2. Li Q, Ritzel RG, McLean LL, McIntosh L, Ko T, Bertrand H, Nargang FE; , Genetics 1996;142:129-140.: Cloning and analysis of the alternative oxidase gene of Neurospora crassa. PUBMED:8770590 EPMC:8770590

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002680

The alternative oxidase is used as a second terminal oxidase in the mitochondria, electrons are transferred directly from reduced ubiquinol to oxygen forming water [PUBMED:8770590]. This is not coupled to ATP synthesis and is not inhibited by cyanide, this pathway is a single step process [PUBMED:9426242]. In Oryza sativa (Rice) the transcript levels of the alternative oxidase are increased by low temperature [PUBMED:9426242]. It has been predicted to contain a coupled diiron centre on the basis of a conserved sequence motif consisting of the proposed iron ligands, four Glu and two His residues [PUBMED:11106766]. The EPR study of Arabidopsis thaliana (Mouse-ear cress) alternative oxidase AOX1a shows that the enzyme contains a hydroxo-bridged mixed-valent Fe(II)/Fe(III) binuclear iron centre [PUBMED:12215444]. A catalytic cycle has been proposed that involves diiron centre and at least one transient protein-derived radical, most probably an invariant Tyr residue [PUBMED:11801238].

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Seed source: Pfam-B_1154 (release 4.2)
Previous IDs: none
Type: Family
Author: Bashton M, Bateman A
Number in seed: 122
Number in full: 1058
Average length of the domain: 197.00 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 65.87 %

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build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.5 22.5
Trusted cut-off 22.5 22.5
Noise cut-off 22.1 22.3
Model length: 215
Family (HMM) version: 13
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the AOX domain has been found. There are 12 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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