Title : The crystal structure of human
dopamine β-hydroxylase at 2.9 Å resolution
Abstract :
- The norepinephrine pathway is believed to modulate behavioral and physiological processes, such as mood, overall arousal, and attention
- Furthermore, abnormalities in the pathway have been linked to numerous diseases, for example hypertension, depression, anxiety, Parkinson's disease, schizophrenia, Alzheimer's disease, attention deficit hyperactivity disorder, and cocaine dependence
- We report the crystal structure of human dopamine β-hydroxylase , which is the enzyme converting dopamine to norepinephrine
- The structure of the DOMON (dopamine β- monooxygenase N-terminal ) domain , also found in >1600 other proteins , reveals a possible metal-binding site and a ligand-binding pocket
- The catalytic core structure shows two different conformations: an open active site , as also seen in another member of this enzyme family [the peptidylglycine α-hydroxylating (and α-amidating) monooxygenase ], and a closed active site structure, in which the two copper-binding sites are only 4 to 5 Å apart, in what might be a coupled binuclear copper site
- The dimerization domain adopts a conformation that bears no resemblance to any other known protein structure
- The structure provides new molecular insights into the numerous devastating disorders of both physiological and neurological origins associated with the dopamine system