Revision as of 21:16, 25 September 2024

Histamine N-methyltransferase (N-term. 6XHIS, TEV)

For information and characterization of this part please see: BBa_K3647666

General information

Histamine N-methyltransferase is one of the two enzymes involved in the metabolism of histamine in mammals, this is known as the N(tau)-methylation pathway. The second pathway is oxidative deamination via diamine oxidase (DAO). This protein is encoded by the gene HNMT and it can be found in the cytosol intracellular fluid. HNMT is expressed in many organs like the liver, kidney, and brain, is found in most of the body tissues, except for serum. (Yoshikawa, 2019)

The function of HNMT is catalyzation of histamine methylation in the presence of S-adenosylmethionine (SAM-e) yielding N-methylhistamine. Histamine (HA) is inactivated by using S-adenosylmethionine (SAM-e) as a methyl donor. This occurs, as an example, during the termination process of neurotransmission actions of HA in the mammalian central nervous system. (Heidari et al, 2015) (Yoshikawa, 2019)

Figure 1. Structure of histamine N-methyltransferase. PBD code 1JQD.

Human Histamine N-methyltransferase is a monomeric protein. It consists of 292 amino acids, of chains A and B, and has a weight of 33.33 kDa. It is a two-domain structure, the large domain is an MTase fold, defined by 20 MTases and the S domain. The MTase domain is the one that participates in histamine binding. The polymorphic amino acid 105 is located on the outer surface of the MTase domain. The HNMT gene is located on chromosome 2q22.1 and has six exons of 50 kb.(Horton, 2001)

HNMT is released via mast cells degranulation upon bronchoconstriction thus contributing to the asthmatic symptoms. The enzyme Histamine N-methyl transferase catalyzes N-methylation which means that it inactivates and degrades histamine. Since histamine is a key ingredient in allergic asthma, it works as a mediator with information from the mast cells. In allergic asthma, IgE antibodies will be released in response to the antibody-mediated cell degranulation. The gene coding for the HNMT protein is stated to be a candidate for inherited asthma due to the human polymorphism and primary biotransformation of histamine in the bronchial epithelium. Histamine N-methyltransferase is one of two enzymes involved in the metabolism of histamine, the second being diamine oxidase. Low levels of HNMT expression in numerous tissues points to an increased risk of asthma development. (Yan, 2000), (Yamauchi, 2019)

Contribution: TERMOSZ-Selye-HUN 2024

Team TERMOSZ-Selye-HUN 2024 took further codon optimisation for the e.coli chassis, and experimented to evaluate whether this had impacted the production or the function of the protein. We have utilised the e.coli strain SixPack for our experiments. Refer to parts BBa_K5492401, BBa_K5492403 and our team wiki here.