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Literature summary extracted from

  • Vendelboe, T.V.; Harris, P.; Zhao, Y.; Walter, T.S.; Harlos, K.; El Omari, K.; Christensen, H.E.
    The crystal structure of human dopamine beta-hydroxylase at 2.9 A resolution (2016), Sci. Adv., 2, e1500980 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.14.17.1 drug development inhibitors of enzyme DBH nepicastat and etamicastat are currently in clinical development for treatment of cocaine dependence Homo sapiens
1.14.17.1 medicine inhibitors of enzyme DBH nepicastat and etamicastat are currently in clinical development for treatment of cocaine dependence Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.17.1 recombinant expression in HEK 293S cells Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.17.1 etamicastat
-
 Homo sapiens
1.14.17.1 nepicastat
-
 Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.17.1 Cu2+ DBH is an ascorbate-dependent glycoprotein that requires two type 2 bound copper ions per subunit to be active. copper sites are labile and termed CuH and CuM, respectively. CuH is coordinated to three histidines and CuM to two histidines and a methionine. CuM is involved in dioxygen binding and is the site for substrate hydroxylation, and CuH is the site of electron transfer Homo sapiens
1.14.17.1 additional information the structure of the common DOMON (dopamine beta-monooxygenase N-terminal) domain reveals a possible metal-binding site and a ligand-binding pocket, coordinating residues are Asp99, Leu100, Ala115, and Asp130 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.17.1 dopamine + ascorbate + O2 Homo sapiens
-
 noradrenaline + dehydroascorbate + H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.17.1 Homo sapiens P09172
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
1.14.17.1 glycoprotein DBH is an ascorbate-dependent glycoprotein, glycosylation is observed at all four predicted sites: Asn64, Asn184, Asn344, and Asn566 Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
1.14.17.1 dopamine + 2 ascorbate + O2 = noradrenaline + 2 monodehydroascorbate + H2O during the reaction, an O atom from molecular O2 is inserted at the beta-carbon in dopamine with retention of configuration, and the second O atom goes to water. The reaction also requires two electrons provided by two ascorbate molecules that are oxidized to semihydroascorbate Homo sapiens
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.17.1 dopamine + ascorbate + O2
-
 Homo sapiens noradrenaline + dehydroascorbate + H2O
-
 ?

Subunits

EC Number Subunits Comment Organism
1.14.17.1 dimer or tetramer the enzyme occurs borh as dimer and tetramer, which can be separated by size exclusion chromatography. The dimer and tetramer do not interconvert in the pH interval pH 4-9. Under denaturing conditions, the tetramer converts to a dimer, and upon addition of a reducing agent, the dimer converts to a monomer. The dimeric structure is asymmetric. In the A chain, the two catalytic CuH and CuM domains are in a closed conformation, and in the B chain, they adopt the same open conformation as seen in peptidylglycine alpha-hydroxylating (and alpha-amidating) monooxygenase (PHM), the catalytic CuH domain in chain A is moved away from the DOMON domain and closer to the catalytic CuM domain. The DOMON domain has an immunoglobulin (Ig)Β–like beta-sandwich structure, the catalytic core (the CuH and CuM domains) has the same topology as the structure of PHM, and the dimerization domains consisting of two antiparallel alpha helices form a four-helix bundle. Following the dimerization domain, there is a beta-strand (residues 561 to 566) taking part in the catalytic CuM domain and a beta-strand (residues 608 to 614) that is part of the DOMON domain, creating a very integrated structure, coordinating residues are Asp99, Leu100, Ala115, and Asp130. The DOMON domain and the dimerization domain are linked via C154-C596. Chain A is linked via two intermolecular disulfide bonds with chain B in the dimerization domain. Enzyme structure analysis, detailed overview Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.14.17.1 DBH
-
 Homo sapiens
1.14.17.1 dopamine beta-hydroxylase
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.17.1 ascorbate DBH is an ascorbate-dependent glycoprotein that requires two type 2 bound copper ions per subunit to be active Homo sapiens

General Information

EC Number General Information Comment Organism
1.14.17.1 evolution DBH is a member of a small unique class of copper-containing hydroxylases that are found in eukaryotes, and all play a critical role in the biosynthesis of neurotransmitters and hormones. The other members of the family are the bifunctional enzyme peptidylglycine alpha-hydroxylating (and alpha-amidating) monooxygenase (PHM), monooxygenase X (DBH-like monooxygenase protein 1, MOXD1), and tyramine beta-monooxygease (TBH), which is the insect homologue of DBH Homo sapiens
1.14.17.1 additional information enzyme structure analysis, detailed overview Homo sapiens
1.14.17.1 physiological function dopamine beta-hydroxylase catalyzes the conversion of dopamine to norepinephrine in the biosynthesis of catecholamines Homo sapiens