Abstract
Dopamine β-monooxygenase (DBM) catalyses the conversion of dopamine to norepinephrine in the catecholamine biosynthetic pathway. The substrate specificity of DBM is wide and the enzyme is capable of performing a variety of oxidations. While the crystal structure of DBM is not yet available, various indirect data allow insight into the enzymes machinery. Considered an attractive therapeutic target for the treatment of hypertension and congestive heart failure, DBM and its inhibitors have received attention by medicinal chemists over the last four decades. Although several QSAR models for DBM inhibitors have been generated, these models are actually unable to explain the exceptionally high potency of the latest generation of inhibitors.
Keywords: Dopamine β-monooxygenase, dopamine β-hydroxylase, inhibitor, imidazolethione, nepicastat, BIA 5-453, CHF
Current Enzyme Inhibition
Title: Dopamine β-Monooxygenase: Mechanism, Substrates and Inhibitors
Volume: 5 Issue: 1
Author(s): Alexandre Beliaev, Humberto Ferreira, David A. Learmonth and Patricio Soares-da-Silva
Affiliation:
Keywords: Dopamine β-monooxygenase, dopamine β-hydroxylase, inhibitor, imidazolethione, nepicastat, BIA 5-453, CHF
Abstract: Dopamine β-monooxygenase (DBM) catalyses the conversion of dopamine to norepinephrine in the catecholamine biosynthetic pathway. The substrate specificity of DBM is wide and the enzyme is capable of performing a variety of oxidations. While the crystal structure of DBM is not yet available, various indirect data allow insight into the enzymes machinery. Considered an attractive therapeutic target for the treatment of hypertension and congestive heart failure, DBM and its inhibitors have received attention by medicinal chemists over the last four decades. Although several QSAR models for DBM inhibitors have been generated, these models are actually unable to explain the exceptionally high potency of the latest generation of inhibitors.
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Cite this article as:
Beliaev Alexandre, Ferreira Humberto, Learmonth A. David and Soares-da-Silva Patricio, Dopamine β-Monooxygenase: Mechanism, Substrates and Inhibitors, Current Enzyme Inhibition 2009; 5 (1) . https://dx.doi.org/10.2174/157340809787314265
DOI https://dx.doi.org/10.2174/157340809787314265 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
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