4zel | pdb_00004zel

Human dopamine beta-hydroxylase

spinqualitylabelsall models 4zel, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zel is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, CU, MAN, NAG Activity: Dopamine beta-monooxygenase, with EC number 1.14.17.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [DOPO_HUMAN] Dopamine beta-hydroxylase deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function [DOPO_HUMAN] Conversion of dopamine to noradrenaline. Publication Abstract from PubMed 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 beta-hydroxylase, which is the enzyme converting dopamine to norepinephrine. The structure of the DOMON (dopamine beta-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 alpha-hydroxylating (and alpha-amidating) monooxygenase], and a closed active site structure, in which the two copper-binding sites are only 4 to 5 A 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. The crystal structure of human dopamine beta-hydroxylase at 2.9 A resolution.,Vendelboe TV, Harris P, Zhao Y, Walter TS, Harlos K, El Omari K, Christensen HE Sci Adv. 2016 Apr 8;2(4):e1500980. doi: 10.1126/sciadv.1500980. eCollection 2016 , Apr. PMID:27152332 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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