Monoamine oxidase

From Proteopedia

Function Monoamine oxidase or amine oxidase (Flavin-containing) (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 or amine oxidase [flavin-containing] 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]. Whole active site. Water molecules are shown as red spheres. Safinamide binding site.

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

3D structures of monoamine oxidase

Updated on 02-July-2023

MAO-A

2z5x, 2bxr, 2bxs – hMAO-A + inhibitor + FAD – human

2z5y - hMAO-A (mutant) + inhibitor + FAD

1o5w - MAO-A + inhibitor + FAD – rat

8eei - CaMAO-A + FAD – Corynebacterium ammoniagenes

8een - CaMAO-A (mutant) + FAD

8eef, 8eeg, 8eeh, 8eek, 8eel, 8eem, 8eeo - CaMAO-A + FAD + amine

8eej - CaMAO-A (mutant) + FAD + amine

MAO-B

1gos – hMAO-B

1oj9, 1oja, 1ojc, 1ojd, 1s2q, 1s2y, 1s3b, 1s3e, 2byb, 2bk3, 2c64, 2c65, 2c66, 2c67, 2vz2, 2vrl, 2vrm, 2v5z, 2v60, 2v61, 2xcg, 2xfn, 2xfp, 2xfq, 2xfu,3po7, 4a7a. 4crt, 5mrl, 6fvz, 6gw0, 6fwc, 6fw0, 6rkb, 6rkp, 6rle, 6yt2, 7b0v, 7b0z, 7p4f, 7p4h, 7zw3– hMAO-B + inhibitor + FAD

2xfo, 2bk4, 2bk5 - hMAO-B (mutant) + inhibitor + FAD

2c72, 2c73, 2c75, 2c76 - hMAO-B (mutant) + FAD

2c70 - hMAO-B + FAD

3zyx - hMAO-B + methylene blue + FAD

MAO-C

3qj4 – hMAO-C + FAD

MAO-N

2vvl, 2vvm, 3zdn – MAO-N (mutant) + FAD – Aspergillus niger

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