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Monoamine oxidase A

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Target not currently curated in GtoImmuPdb

Target id: 2489

Nomenclature: Monoamine oxidase A

Abbreviated Name: MAO-A

Family: Catecholamine turnover

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 527 Xp11.4-p11.3 MAOA monoamine oxidase A
Mouse - 526 X A2 Maoa monoamine oxidase A
Rat - 526 Xq12 Maoa monoamine oxidase A
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human Monoamine Oxidase A with Harmine
PDB Id:  2Z5X
Ligand:  harmine
Resolution:  2.2Å
Species:  Human
References:  9
Enzyme Reaction Click here for help
EC Number: 1.4.3.4
Description Reaction Reference
Dopamine -> 3,4-dihydroxyphenylacetaldehyde + NH3
(-)-Noradrenaline -> 3,4-dihydroxymandelic acid + NH3
(-)-Adrenaline -> 3,4-dihydroxymandelic acid + NH3
5-Hydroxytryptamine -> 5-hydroxyindole acetaldehyde + NH3
Tyramine -> 4-hydroxyphenyl acetaldehyde + NH3
Cofactors Click here for help
Cofactor Species Comments Reference
flavin adenine dinucleotide Human

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
moclobemide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pKi 5
pKi 8.3 (Ki 5x10-9 M) [5]
phenelzine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Irreversible inhibition 7.3 pKi 2
pKi 7.3 (Ki 4.7x10-8 M) [2]
selegiline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 4.2 pKi 7
pKi 4.2 (Ki 6.725x10-5 M) [7]
CR4056 Small molecule or natural product Hs Inhibition 6.7 pIC50 4
pIC50 6.7 (IC50 2.027x10-7 M) [4]
Description: Inhibition of recombinant human MAO-A activity in vitro.
tranylcypromine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 4.7 pIC50 11
pIC50 4.7 (IC50 2x10-5 M) [11]
linezolid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.3 pIC50 8
pIC50 4.3 (IC50 4.6x10-5 M) [8]
clorgiline Small molecule or natural product Ligand has a PDB structure Hs Inhibition - -
befloxatone Small molecule or natural product Hs Inhibition - - 3
[3]
pirlindole Small molecule or natural product Approved drug Hs Inhibition - - 6
[6]
Inhibitor Comments
Differential inhibition of the A or B isozymes of MAO have different clinical outcomes. Inhibition of MAOA results in antidepressant activity [1], whereas inhibition of MAOB results in antiparkinsonian activity [10]. Important substrates for MAO activity in the CNS include dopamine, adrenaline, noradrenaline, serotonin (5-HT), and β-phenylethylamine.
Tranylcypromine is an irreversible MAO inhibitor with equal potency for the A and B isozymes [11].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Brunner syndrome
Synonyms: Monoamine oxidase A deficiency [Orphanet: ORPHA3057]
OMIM: 300615
Orphanet: ORPHA3057

References

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1. Binda C, Hubálek F, Li M, Herzig Y, Sterling J, Edmondson DE, Mattevi A. (2004) Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J. Med. Chem., 47 (7): 1767-74. [PMID:15027868]

2. Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmondson DE. (2008) Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry, 47 (20): 5616-25. [PMID:18426226]

3. Curet O, Damoiseau-Ovens G, Sauvage C, Sontag N, Avenet P, Depoortere H, Caille D, Bergis O, Scatton B. (1998) Preclinical profile of befloxatone, a new reversible MAO-A inhibitor. J Affect Disord, 51 (3): 287-303. [PMID:10333983]

4. Ferrari F, Fiorentino S, Mennuni L, Garofalo P, Letari O, Mandelli S, Giordani A, Lanza M, Caselli G. (2011) Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain. J Pain Res, 4: 111-25. [PMID:21647215]

5. Jagrat M, Behera J, Yabanoglu S, Ercan A, Ucar G, Sinha BN, Sankaran V, Basu A, Jayaprakash V. (2011) Pyrazoline based MAO inhibitors: synthesis, biological evaluation and SAR studies. Bioorg. Med. Chem. Lett., 21 (14): 4296-300. [PMID:21680183]

6. Medvedev AE, Shvedov VI, Chulkova TM, Fedotova OA, Saederup E, Squires RF. (1998) The influence of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase A and GABAA receptor binding. J. Neural Transm. Suppl., 52: 337-42. [PMID:9564636]

7. Mishra N, Sasmal D. (2011) Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation. Bioorg. Med. Chem. Lett., 21 (7): 1969-73. [PMID:21377879]

8. Phillips OA, D'Silva R, Bahta TO, Sharaf LH, Udo EE, Benov L, Eric Walters D. (2015) Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives. Eur J Med Chem, 106: 120-31. [PMID:26536532]

9. Son SY, Ma J, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T. (2008) Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors. Proc. Natl. Acad. Sci. U.S.A., 105 (15): 5739-44. [PMID:18391214]

10. Tetrud JW, Langston JW. (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science, 245 (4917): 519-22. [PMID:2502843]

11. Yoshida S, Rosen TC, Meyer OG, Sloan MJ, Ye S, Haufe G, Kirk KL. (2004) Fluorinated phenylcyclopropylamines. Part 3: Inhibition of monoamine oxidase A and B. Bioorg. Med. Chem., 12 (10): 2645-52. [PMID:15110846]

How to cite this page

Catecholamine turnover: Monoamine oxidase A. Last modified on 07/05/2020. Accessed on 27/10/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2489.