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The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase

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Abstract

Semicarbazide-sensitive amine oxidases (SSAOs) catalyze oxidative deamination of primary amines, but the true physiological function of these enzymes is still poorly understood. Here, we have studied the functional and structural characteristics of a human cell-surface SSAO, AOC2, which is homologous to the better characterized family member, AOC3. The preferred in vitro substrates of AOC2 were found to be 2-phenylethylamine, tryptamine and p-tyramine instead of methylamine and benzylamine, the favored substrates of AOC3. Molecular modeling suggested structural differences between AOC2 and AOC3, which provide AOC2 with the capability to use the larger monoamines as substrates. Even though AOC2 mRNA was expressed in many tissues, the only tissues with detectable AOC2-like enzyme activity were found in the eye. Characterization of AOC2 will help in evaluating the contribution of this enzyme to the pathological processes attributed to the SSAO activity and in designing specific inhibitors for the individual members of the SSAO family.

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Acknowledgments

The expert technical assistance of Teija Pöysti, Maritta Pohjansalo, Pirjo Heinilä, Etta-Liisa Väänänen, Riikka Sjöroos, Sari Mäki, and Laila Reunanen is greatly appreciated. Drs. Heikki Irjala and Kalle Alanen are thanked for providing us with the tissue samples. Dr. Gennady Yegutkin is thanked for advice. Professor Mark Johnson is acknowledged for the excellent facilities at the Structural Bioinformatics Laboratory at the Department of Biochemistry and Pharmacy, Åbo Akademi University. This work was supported by the Academy of Finland, the Sigrid Juselius Foundation, the Emil Aaltonen Foundation, and the Varsinais-Suomi Regional Fund of the Finnish Cultural Foundation.

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Authors and Affiliations

  1. MediCity Research Laboratory, University of Turku, and National Institute for Health and Welfare, Tykistökatu 6, 20520, Turku, Finland

    Sam Kaitaniemi, Heli Elovaara, Kirsi Grön, Marko Salmi, Sirpa Jalkanen & Kati Elima

  2. Department of Biochemistry and Pharmacy, Åbo Akademi University, 20520, Turku, Finland

    Heidi Kidron & Tiina Salminen

  3. Department of Ophthalmology, Turku University Hospital, 20521, Turku, Finland

    Janne Liukkonen

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  1. Sam Kaitaniemi
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Correspondence to Kati Elima.

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18_2009_76_MOESM1_ESM.ppt

Supplemental Figure 1. Sequence alignment of mammalian monoamine oxidazing SSAOs. The deduced amino acid sequences of four monoamine oxidizing mammalian SSAOs from GenBank were compared. The SSAOs shown are human AOC3 (VAP-1, AF067406), mouse AOC3 (mAOC3, mVAP-1, AF054831), human AOC2 (hRAO, D88213) and Bovine Serum Amine Oxidase (BSAO, L27218). Highlighted are: yellow, the hydrophobic N-terminal sequence; red, the conserved signature motif of SSAO active site, where the first tyrosine is post-translationally modified to topaquinone; pink, (putative) catalytic site base; light green, the conserved, Cu(II) binding histidine residues; turquoise, the conserved cysteine residues involved in dimerization; dark blue the putative N-linked glycosylation sites. The RGD sequence of AOC3 is indicated with red letters. The underlined sequence corresponds to the region deleted in the AOC2 splice variant 2 (sv2). For review of the consensus sites important for SSAO activity, see [39]. (PPT 55 kb)

18_2009_76_MOESM2_ESM.tif

Supplemental Figure 2. Antibodies recognizing AOC3 alone or both AOC3 and AOC2 give identical staining patterns. Frozen sections of human tonsil were stained with the monoclonal antibody 2D10 detecting only AOC3 (left panel) and with the polyclonal antibody poly-VAP detecting both AOC2 and AOC3 (right panel). Scale bar 100 μm. (TIFF 15356 kb)

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Kaitaniemi, S., Elovaara, H., Grön, K. et al. The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase. Cell. Mol. Life Sci. 66, 2743–2757 (2009). https://doi.org/10.1007/s00018-009-0076-5

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