Monoamine oxidase B

Target id: 2490

Nomenclature: Monoamine oxidase B

Abbreviated Name: MAO-B

Family: Catecholamine turnover

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Monoamine oxidase B in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 520 Xp11.4-p11.3 MAOB monoamine oxidase B
Mouse - 520 X A1.2 Maob monoamine oxidase B
Rat - 520 Xq12 Maob monoamine oxidase B
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human monoamine oxidase B in complex with the multi-target inhibitor ASS234
PDB Id:  4CRT
Ligand:  ASS234
Resolution:  1.8Å
Species:  Human
References:  4
Enzyme Reaction
EC Number: 1.4.3.4
Cofactors
Cofactor Species Comments Reference
flavin adenine dinucleotide Human

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
phenelzine Hs Irreversible inhibition 7.8 pKi 2
pKi 7.8 (Ki 1.5x10-8 M) [2]
lazabemide Hs Inhibition 7.1 pKi 6,11
pKi 7.1 (Ki 8.4x10-8 M) [6,11]
safinamide Hs Inhibition 6.3 pKi 1
pKi 6.3 (Ki 4.5x10-7 M) [1]
moclobemide Hs Inhibition 6.0 pKi 7
pKi 6.0 (Ki 1.08x10-6 M) [7]
selegiline Hs Inhibition 5.7 – 6.0 pKi 3,9
pKi 5.7 – 6.0 (Ki 1.96x10-6 – 9.7x10-7 M) [3,9]
safinamide Hs Inhibition 8.1 pIC50 8
pIC50 8.1 (IC50 7.7x10-9 M) [8]
rasagiline Hs Inhibition 7.8 pIC50 13
pIC50 7.8 (IC50 1.4x10-8 M) [13]
pargyline Rn Inhibition 5.7 pIC50 5
pIC50 5.7 (IC50 1.8x10-6 M) [5]
tranylcypromine Hs Inhibition 4.7 pIC50 12
pIC50 4.7 (IC50 1.9x10-5 M) [12]
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 [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 [12].

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. Biochemistry47 (20): 5616-25. [PMID:18426226]

3. Di Santo R, Costi R, Roux A, Artico M, Befani O, Meninno T, Agostinelli E, Palmegiani P, Turini P, Cirilli R et al.. (2005) Design, synthesis, and biological activities of pyrrolylethanoneamine derivatives, a novel class of monoamine oxidases inhibitors. J. Med. Chem.48 (13): 4220-3. [PMID:15974574]

4. Esteban G, Allan J, Samadi A, Mattevi A, Unzeta M, Marco-Contelles J, Binda C, Ramsay RR. (2014) Kinetic and structural analysis of the irreversible inhibition of human monoamine oxidases by ASS234, a multi-target compound designed for use in Alzheimer's disease. Biochim. Biophys. Acta,  [Epub ahead of print]. [PMID:24642166]

5. Fowler CJ, Mantle TJ, Tipton KF. (1982) The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, l-deprenyl and pargyline. Biochem. Pharmacol.31 (22): 3555-61. [PMID:6817759]

6. Haefely WE, Kettler R, Keller HH, Da Prada M. (1990) Ro 19-6327, a reversible and highly selective monoamine, oxidase B inhibitor: a novel tool to explore the MAO-B function in humans. Adv Neurol53: 505-12. [PMID:2122653]

7. 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]

8. Koch P, Akkari R, Brunschweiger A, Borrmann T, Schlenk M, Küppers P, Köse M, Radjainia H, Hockemeyer J, Drabczyńska A et al.. (2013) 1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases. Bioorg. Med. Chem.21 (23): 7435-52. [PMID:24139167]

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. Tetrud JW, Langston JW. (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science245 (4917): 519-22. [PMID:2502843]

11. Toprakçí M, Yelekçi K. (2005) Docking studies on monoamine oxidase-B inhibitors: estimation of inhibition constants (K(i)) of a series of experimentally tested compounds. Bioorg. Med. Chem. Lett.15 (20): 4438-46. [PMID:16137882]

12. 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]

13. Youdim MB, Gross A, Finberg JP. (2001) Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br. J. Pharmacol.132 (2): 500-6. [PMID:11159700]

How to cite this page

Catecholamine turnover: Monoamine oxidase B. Last modified on 09/04/2015. Accessed on 19/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2490.