histamine N-methyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: S-adenosyl-L-methionine(1+) + histamine = N(tau)-methylhistamine + S-adenosyl-L-homocysteine + H+. [EC:2.1.1.8, RHEA:19301]

Histamine N-methyltransferase (HNMT) is a key enzyme involved in the inactivation of histamine, a biogenic amine that plays a vital role in various physiological processes, including allergic reactions, inflammation, and neurotransmission. HNMT catalyzes the transfer of a methyl group from S-adenosyl methionine (SAM) to the nitrogen atom at position 1 of histamine, resulting in the formation of N-methylhistamine. This methylation reaction effectively terminates histamine's activity by reducing its affinity for histamine receptors.

HNMT's molecular function is primarily centered around the catalytic transfer of a methyl group. It achieves this by employing a mechanism that involves the formation of a transient covalent intermediate between the enzyme and SAM. This intermediate facilitates the transfer of the methyl group to the target molecule, histamine.

The process begins with the binding of both SAM and histamine to the active site of HNMT. The enzyme then facilitates the formation of a covalent bond between the methyl group of SAM and a cysteine residue within the active site. This covalent intermediate represents a key step in the methylation reaction, as it positions the methyl group for transfer to the target histamine molecule.

Following the formation of the intermediate, histamine undergoes a nucleophilic attack on the methyl group, displacing the enzyme and resulting in the formation of N-methylhistamine. Simultaneously, the enzyme releases S-adenosyl homocysteine (SAH), the demethylated product of SAM.

The efficiency and specificity of HNMT's catalytic activity are influenced by the enzyme's structure and the properties of its active site. HNMT exhibits a highly conserved active site, which contains residues critical for the binding of both SAM and histamine, as well as the formation of the covalent intermediate.

In summary, HNMT's molecular function lies in its ability to catalyze the methylation of histamine, effectively rendering it inactive. This methylation reaction, driven by the transfer of a methyl group from SAM, involves the formation of a transient covalent intermediate between the enzyme and SAM. HNMT's role in histamine inactivation is crucial for regulating histamine's diverse physiological functions, including its involvement in allergic reactions, inflammation, and neurotransmission.'
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Proteins (2)

Compounds (5)