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The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the mitochondrial outer membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important role in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine. Like MAOA, it also degrades dopamine.
Edmondson et al. described structural features of the human enzyme: it has a hydrophobic bipartite elongated cavity that (for the "open" conformation) occupies a combined volume close to 700 Å3. hMAO-A has a single cavity that exhibits a rounder shape and is larger in volume than the "substrate cavity" of hMAO-B.
The first cavity of hMAO-B has been termed the entrance cavity (290 Å3), the second substrate cavity or active site cavity (~390 Å3) – between both an isoleucine199 side chain serves as a gate. Depending on the substrate or bound inhibitor, it can exist in either an open or a closed form which has been shown to be important in defining the inhibitor specificity of hMAO B. At the end of the substrate cavity is the FAD coenzyme with sites for favorable amine binding about the flavin involving two nearly parallel tyrosyl (398 and 435) residues that form what has been termed an aromatic cage.
Differences between MAOA and MAOBEdit
Generally, Monoamine Oxidase A (MAOA) prefers to metabolize norepinephrine (NE), serotonin (5-HT), and Dopamine (DA) (and other less clinically relevant chemicals). Monoamine Oxidase B, on the other hand, prefers to metabolize Dopamine (DA) (and other less clinically relevant chemicals).The differences between the substrate selectivity of the two enzymes are utilized clinically when treating specific disorders: Monoamine Oxidase A inhibitors have been used in the treatment of depression, and Monoamine Oxidase B inhibitors are used in the treatment of Parkinson's Disease.
Species-dependent divergences may hamper the extrapolation of inhibitor potencies.
- Safinamide and isoquinoline-analogs
- Certain umbelliferone ethers including geiparvarin
- (E,E)-8-(4-phenylbutadien-1-yl)caffeines, with A2A antagonistic component
- Substituted chalcones
- Desmethoxyyangonin, a constituent of kava-kava extract; modest affinity
- ↑ Entrez Gene: MAOB monoamine oxidase B.
- ↑ 2.0 2.1 Edmondson DE, Binda C, Mattevi A (2007). Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B. Archives of Biochemistry and Biophysics 464 (2): 269–76.
- ↑ 3.0 3.1 Novaroli L, Daina A, Favre E, et al. (October 2006). Impact of species-dependent differences on screening, design, and development of MAO B inhibitors. Journal of Medicinal Chemistry 49 (21): 6264–72.
- ↑ Leonetti F, Capaldi C, Pisani L, Nicolotti O, Muncipinto G, Stefanachi A, Cellamare S, Caccia C, Carotti A (October 2007). Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase. Journal of Medicinal Chemistry 50 (20): 4909–16.
- ↑ Binda C, Wang J, Pisani L, Caccia C, Carotti A, Salvati P, Edmondson DE, Mattevi A (2007). Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. Journal of Medicinal Chemistry 50 (23): 5848–52.
- ↑ Catto M, Nicolotti O, Leonetti F, Carotti A, Favia AD, Soto-Otero R, Méndez-Alvarez E, Carotti A (2006). Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted coumarins from ligand- and target-based approaches. Journal of Medicinal Chemistry 49 (16): 4912–25.
- ↑ Carotti A, Carrieri A, Chimichi S, Boccalini M, Cosimelli B, Gnerre C, Carotti A, Carrupt PA, Testa B (December 2002). Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies. Bioorg. Med. Chem. Lett. 12 (24): 3551–5.
- ↑ Pretorius J, Malan SF, Castagnoli N, Bergh JJ, Petzer JP (September 2008). Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues. Bioorganic & Medicinal Chemistry 16 (18): 8676–84.
- ↑ Carotti A, Catto M, Leonetti F, Campagna F, Soto-Otero R, Méndez-Alvarez E, Thull U, Testa B, Altomare C (November 2007). Synthesis and monoamine oxidase inhibitory activity of new pyridazine-, pyrimidine- and 1,2,4-triazine-containing tricyclic derivatives. Journal of Medicinal Chemistry 50 (22): 5364–71.
- ↑ Chimenti F, Fioravanti R, Bolasco A, et al. (May 2009). Chalcones: a valid scaffold for monoamine oxidases inhibitors. J. Med. Chem. 52 (9): 2818–24.
- ↑ Uebelhack R, Franke L, Schewe HJ (September 1998). Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry 31 (5): 187–92.
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- Bonaldo MF, Lennon G, Soares MB (1997). Normalization and subtraction: two approaches to facilitate gene discovery.. Genome Res. 6 (9): 791–806.
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- Checkoway H, Franklin GM, Costa-Mallen P, et al. (1998). A genetic polymorphism of MAO-B modifies the association of cigarette smoking and Parkinson's disease.. Neurology 50 (5): 1458–61.
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