Biomaterial Database

Affinity labeling of catechol O-methyltransferase by N-haloacetyl derivatives of 3,5-dimethoxy-4-hydroxyphenylethylamine and 3,4-dimethoxy-5-hydroxyphenylethylamine. Kinetics of inactivation. 1975

R T Borchardt, and D R Thakker

In an attempt to elucidate the relationship between the chemical structure and the catalytic function of catechol O-methyltransferase (COMT), several classes of affinity labeling reagents have been synthesized and their interaction with COMT has been studied. Earlier studies have shown that various N-haloacetyl derivatives of 3,5-dimethoxy-4-hydroxyphenylethylamine were effective affinity labeling reagents for this enzyme. In this report we have shown that N-haloacetyl derivatives of the isomeric 3,4-dimethoxy-5-hydroxyphenylethylamine also rapidly and irreversibly inactivate COMT ant they satisfy many of the criteria established for affinity labeling reagents. This latter group of agents appear to modify a nucleophilic residue at the active site of COMT different from that modified by the 3,5-dimethoxy-4-hydroxyphenylethylamine series. Evidence to support this conclusion has been obtained by comparing the kinetics of COMT inactivation and the substrate protection profiles for these two classes of affinity labeling reagents.

UI	MeSH Term	Description	Entries
D007461	Iodoacetates	Iodinated derivatives of acetic acid. Iodoacetates are commonly used as alkylating sulfhydryl reagents and enzyme inhibitors in biochemical research.	Iodoacetic Acids,Acids, Iodoacetic
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008433	Mathematics	The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Mathematic
D010627	Phenethylamines	A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)	Phenylethylamines
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
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D002394	Catechol O-Methyltransferase	Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.	Catechol Methyltransferase,Catechol-O-Methyltransferase,Catechol O Methyltransferase,Methyltransferase, Catechol,O-Methyltransferase, Catechol
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations