Biomaterial Database

Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines: evidence for a novel regulatory mechanism. 1998

A J Ramsey, and P F Fitzpatrick

Department of Biochemistry, Texas A&M University, College Station 77843-2128, USA.

The effects of phosphorylation at Ser40 of rat tyrosine hydroxylase on the affinities of catechols have been determined with both the ferric and ferrous forms of the enzyme. Phosphorylation had no effect on the Ki value for the inhibition of the ferrous enzyme by either dopamine or DOPA when the initial rate of turnover was measured in assays. However, phosphorylation of the ferric enzyme resulted in a 17-fold decrease in affinity for DOPA and a 300-fold decrease in the affinity for dopamine, while the affinity for dihydroxynaphthalene was unchanged. The changes in binding affinity for the two catecholamines were almost exclusively due to large increases in the dissociation rate constants upon phosphorylation. These results support a novel mechanism for regulation in which phosphorylation affects binding of catecholamines to the catalytically inactive ferric form of the tyrosine hydroxylase.

UI	MeSH Term	Description	Entries
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011499	Protein Processing, Post-Translational	Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.	Amino Acid Modification, Post-Translational,Post-Translational Modification,Post-Translational Protein Modification,Posttranslational Modification,Protein Modification, Post-Translational,Amino Acid Modification, Posttranslational,Post-Translational Amino Acid Modification,Post-Translational Modifications,Post-Translational Protein Processing,Posttranslational Amino Acid Modification,Posttranslational Modifications,Posttranslational Protein Processing,Protein Processing, Post Translational,Protein Processing, Posttranslational,Amino Acid Modification, Post Translational,Modification, Post-Translational,Modification, Post-Translational Protein,Modification, Posttranslational,Modifications, Post-Translational,Modifications, Post-Translational Protein,Modifications, Posttranslational,Post Translational Amino Acid Modification,Post Translational Modification,Post Translational Modifications,Post Translational Protein Modification,Post Translational Protein Processing,Post-Translational Protein Modifications,Processing, Post-Translational Protein,Processing, Posttranslational Protein,Protein Modification, Post Translational,Protein Modifications, Post-Translational
D002395	Catecholamines	A general class of ortho-dihydroxyphenylalkylamines derived from TYROSINE.	Catecholamine,Sympathin,Sympathins
D004295	Dihydroxyphenylalanine	A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.	Dopa,3,4-Dihydroxyphenylalanine,3-Hydroxy-DL-tyrosine,Dihydroxyphenylalanine Hydrochloride, (2:1),beta-Hydroxytyrosine,3 Hydroxy DL tyrosine,3,4 Dihydroxyphenylalanine,beta Hydroxytyrosine
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005290	Ferric Compounds	Inorganic or organic compounds containing trivalent iron.	Compounds, Ferric
D005296	Ferrous Compounds	Inorganic or organic compounds that contain divalent iron.	Compounds, Ferrous
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia