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Biological Chemistry

Structure of enzyme that converts neurotransmitter dopamine to norepinephrine revealed for the first time

Structure could inspire new drugs that target the enzyme, which plays a role in depression, Tourette syndrome, heart failure, and other ailments

by Sarah Everts
April 11, 2016 | A version of this story appeared in Volume 94, Issue 15

Credit: AAAS 2016
The active site of human dopamine ß-hydroxylase features two closely spaced catalytic copper atoms.
Image of human dopamine β-hydroxylase.
Credit: AAAS 2016
The active site of human dopamine ß-hydroxylase features two closely spaced catalytic copper atoms.

A first glimpse of the three-dimensional structure of the human enzyme that converts the neurotransmitter dopamine to norepinephrine comes courtesy of X-ray crystallography and a team led by Hans E. M. Christensen of the Technical University of Denmark (Sci. Adv. 2016, DOI: 10.1126/sciadv.1500980). The enzyme, dopamine β-hydroxylase, modulates the relative brain concentrations of dopamine and norepinephrine. That balance has been implicated in a large number of physiological, neurological, and psychiatric diseases, Christensen notes. Examples include congestive heart failure, hypertension, Alzheimer’s and Parkinson’s diseases, and depression. The structure of the human enzyme, which has been determined at a resolution of 2.9 Å, is the first of its kind for any organism. It shows the enzyme can adopt open and closed conformations and features a catalytic site with two copper atoms about 4 Å apart in the closed conformation. The proximity of the copper atoms is a welcome surprise, Christensen says, because prior studies placed the catalytically important metals about 14 Å apart. Disrupting the closed conformation with small molecules might offer a new strategy for drug developers devising therapeutics aimed at the enzyme.


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