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Catechol-O-methyltransferase

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Target not currently curated in GtoImmuPdb

Target id: 2472

Nomenclature: Catechol-O-methyltransferase

Abbreviated Name: COMT

Family: Catecholamine turnover

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 271 22q11.21 COMT catechol-O-methyltransferase
Mouse 1 265 16 11.4 cM Comt catechol-O-methyltransferase
Rat 1 264 11q23 Comt catechol-O-methyltransferase
Previous and Unofficial Names Click here for help
Comt1
Database Links Click here for help
BRENDA
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 2.1.1.6 S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
Description Reaction Reference
(-)-Noradrenaline -> normetanephrine
(-)-Adrenaline -> metanephrine
3,4-Dihydroxymandelic acid -> vanillylmandelic acid
Dopamine -> 3-methoxytyramine
Cofactors Click here for help
Cofactor Species Comments Reference
S-adenosyl methionine 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
tolcapone Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.5 – 9.6 pKi 3
pKi 9.6 (Ki 2.7x10-10 M) soluble enzyme [3]
Description: soluble enzyme
pKi 9.5 (Ki 2.9x10-10 M) membrane-bound enzyme [3]
Description: membrane-bound enzyme
entacapone Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.7 – 9.5 pKi 3
pKi 9.5 (Ki 3x10-10 M) soluble enzyme [3]
Description: soluble enzyme
pKi 8.7 (Ki 2x10-9 M) membrane-bound enzyme [3]
Description: membrane-bound enzyme
opicapone Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 9.0 pKi 2
pKi 9.0 (Ki 1x10-9 M) [2]
opicapone Small molecule or natural product Approved drug Mm Inhibition 8.8 pKi 2
pKi 8.8 (Ki 1.5x10-9 M) [2]
opicapone Small molecule or natural product Approved drug Rn Inhibition 8.8 pKi 2
pKi 8.8 (Ki 1.5x10-9 M) [2]
View species-specific inhibitor tables
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Alcohol dependence
Disease Ontology: DOID:0050741
OMIM: 103780
Disease:  DiGeorge syndrome
Disease Ontology: DOID:11198
OMIM: 188400
Orphanet: ORPHA567
Disease:  Panic disorder 1; PAND1
Disease Ontology: DOID:594
OMIM: 167870
Disease:  Schizophrenia
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
Disease:  Velocardiofacial syndrome
Disease Ontology: DOID:12583
OMIM: 192430
Orphanet: ORPHA567
General Comments
SARS-CoV-2/COVID-19
Experimental in vitro evidence, using affinity-purification mass spectrometry (AP-MS), indicates a protein-protein interaction between COMT and the SARS-CoV-2 non-structural protein 7 (Nsp7) [1], although whether this interaction is realistic based on spatial distribution of the host and viral proteins within cells was not addressed in this study. Speculatively, COMT ligands such as entacapone could be utilised to examine the effect of inhibiting the COMT/Nsp7 protein-protein interaction on SARS-CoV-2 pathobiology.

References

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1. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583 (7816): 459-468. [PMID:32353859]

2. Lanier M, Ambrus G, Cole DC, Davenport R, Ellery J, Fosbeary R, Jennings AJ, Kadotani A, Kamada Y, Kamran R et al.. (2014) A fragment-based approach to identifying S-adenosyl-l-methionine -competitive inhibitors of catechol O-methyl transferase (COMT). J Med Chem, 57 (12): 5459-63. [PMID:24847974]

3. Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melén K, Julkunen I, Taskinen J. (1995) Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry, 34 (13): 4202-10. [PMID:7703232]

How to cite this page

Catecholamine turnover: Catechol-O-methyltransferase. Last modified on 27/03/2020. Accessed on 22/06/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2472.