Monoamine oxidase

From Proteopedia

Revision as of 10:44, 23 May 2016

spinqualitylabelsall models Human MAO-B complex with safinamide and FAD (PDB entry 2v5z) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Monoamine oxidase (MAO) are enzymes which catalyze the oxidation of monoamines[1]. MAO contains FAD as co-factor. MAO-A and MAO-C are human enzymes which oxidize adrenaline, noradrenaline, serotonin and dopamine. MAO-B is a human enzyme which oxidizes benzylamine and phenylethylamine. For details on MAO-B see Monoamine oxidase b. MAO-N is a Aspergillus niger enzyme which oxidizes primary amines[2]. Relevance Elevated levels of MAO-A in the brain are measured during depression[3]. MAO inhibitors were the first anti-depression drugs developed. Structural highlights MAO-B active site is composed of 2 cavities: the substrate cavity in front of the FAD and the entrance cavity. Safinamide - a drug tested for Parkinson's disease[4] - occupies both cavities[5]. . Water molecules shown as red spheres.

3D structures of monoamine oxidase

Updated on 23-May-2016

References

1. ↑ Tipton KF, Boyce S, O'Sullivan J, Davey GP, Healy J. Monoamine oxidases: certainties and uncertainties. Curr Med Chem. 2004 Aug;11(15):1965-82. PMID:15279561
2. ↑ Atkin KE, Reiss R, Koehler V, Bailey KR, Hart S, Turkenburg JP, Turner NJ, Brzozowski AM, Grogan G. The structure of monoamine oxidase from Aspergillus niger provides a molecular context for improvements in activity obtained by directed evolution. J Mol Biol. 2008 Dec 31;384(5):1218-31. Epub 2008 Oct 14. PMID:18951902 doi:10.1016/j.jmb.2008.09.090
3. ↑ Meyer JH, Ginovart N, Boovariwala A, Sagrati S, Hussey D, Garcia A, Young T, Praschak-Rieder N, Wilson AA, Houle S. Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. Arch Gen Psychiatry. 2006 Nov;63(11):1209-16. PMID:17088501 doi:http://dx.doi.org/10.1001/archpsyc.63.11.1209
4. ↑ Caccia C, Maj R, Calabresi M, Maestroni S, Faravelli L, Curatolo L, Salvati P, Fariello RG. Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology. 2006 Oct 10;67(7 Suppl 2):S18-23. PMID:17030736
5. ↑ Binda C, Wang J, Pisani L, Caccia C, Carotti A, Salvati P, Edmondson DE, Mattevi A. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem. 2007 Nov 15;50(23):5848-52. Epub 2007 Oct 4. PMID:17915852 doi:http://dx.doi.org/10.1021/jm070677y