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Monoamine oxidase A

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Target id: 2489

Nomenclature: Monoamine oxidase A

Abbreviated Name: MAO-A

Family: Catecholamine turnover

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 527 Xp11.3 MAOA monoamine oxidase A
Mouse 1 526 X 11.78 cM Maoa monoamine oxidase A
Rat - 526 Xq11 Maoa monoamine oxidase A
Database Links Click here for help
Alphafold P21397 (Hs), Q64133 (Mm), G3V9Z3 (Rn)
BRENDA 1.4.3.4
CATH/Gene3D 3.50.50.60
ChEMBL Target CHEMBL1951 (Hs), CHEMBL3681 (Mm)
DrugBank Target P21397 (Hs)
Ensembl Gene ENSG00000189221 (Hs), ENSMUSG00000025037 (Mm), ENSRNOG00000002848 (Rn)
Entrez Gene 4128 (Hs), 17161 (Mm), 29253 (Rn)
Human Protein Atlas ENSG00000189221 (Hs)
KEGG Enzyme 1.4.3.4
KEGG Gene hsa:4128 (Hs), mmu:17161 (Mm), rno:29253 (Rn)
Pharos P21397 (Hs)
RefSeq Nucleotide NM_000240 (Hs), NM_001270458 (Hs), NM_173740 (Mm), NM_033653 (Rn)
RefSeq Protein NP_001257387 (Hs), NP_000231 (Hs), NP_776101 (Mm), NP_387502 (Rn)
SynPHARM 78568 (in complex with clorgiline)
UniProtKB P21397 (Hs), Q64133 (Mm), G3V9Z3 (Rn)
Wikipedia MAOA (Hs)
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:  12
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

Download all structure-activity data for this target as a CSV file go icon to follow link

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]
bifemelane Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.4 pKi 10
⤷ pKi 5.4 (Ki 4.2x10-6 M) [10]
Description: Inhibition of monoamine oxidase (MAO) in human brain synaptosomes
selegiline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 4.2 pKi 9
⤷ pKi 4.2 (Ki 6.725x10-5 M) [9]
harmaline Small molecule or natural product Mm Inhibition 7.9 pIC50 7
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [7]
Description: Inhibition of MAOA activity in mouse brain
harmaline Small molecule or natural product Hs Inhibition 7.5 pIC50 6
⤷ pIC50 7.5 (IC50 3.29x10-8 M) [6]
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 14
⤷ pIC50 4.7 (IC50 2x10-5 M) [14]
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 11
⤷ pIC50 4.3 (IC50 4.6x10-5 M) [11]
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 - - 8
⤷ [8]
View species-specific inhibitor tables
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 [13]. 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 [14].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
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. Jismy B, El Qami A, Pišlar A, Frlan R, Kos J, Gobec S, Knez D, Abarbri M. (2021) Pyrimido[1,2-b]indazole derivatives: Selective inhibitors of human monoamine oxidase B with neuroprotective activity. Eur J Med Chem, 209: 112911. [PMID:33071056]

7. Lebreton L, Curet O, Gueddari S, Mazouz F, Bernard S, Burstein C, Milcent R. (1995) Selective and potent monoamine oxidase type B inhibitors: 2-substituted 5-aryltetrazole derivatives. J Med Chem, 38 (24): 4786-92. [PMID:7490728]

8. 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]

9. 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]

10. Naoi M, Nomura Y, Ishiki R, Suzuki H, Nagatsu T. (1988) 4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy)-N-methylalkylamines as new inhibitors of type A and B monoamine oxidase. J Neurochem, 50 (1): 243-7. [PMID:3335842]

11. 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]

12. 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 USA, 105 (15): 5739-44. [PMID:18391214]

13. 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]

14. 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 05/02/2024. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2489.