HNMT is a cytoplasmic protein, meaning that it operates within the cytoplasm of a cell. The cytoplasm fills the space between the outer cell membrane (also known as the cellular plasma membrane) and the nuclear membrane (which surrounds the cell's nucleus). HNMT helps regulate histamine levels by degrading histamine within the cytoplasm, ensuring proper cellular function.
Proteins consist of amino acid residues and form a three-dimensional structure. The crystallographic structure to depict the three-dimensional structure of human HNMT protein was first described in 2001 as a monomeric protein that has a mass of 33 kilodaltons and consists of two structural domains.
The first domain, called the "MTase domain", contains the active site where methylation occurs. It has a classic fold found in many other methyltransferases and consists of a seven-stranded beta-sheet surrounded by three helices on each side. This domain binds to its cofactor, S-adenosyl--methionine (SAM-e), which provides the methyl group for N-methylation reactions.
The second domain, called the "substrate binding domain", interacts with histamine, contributing to its binding to the enzyme molecule. This domain is connected to the MTase domain and forms a separate region. It includes an anti-parallel beta sheet along with additional alpha helices and 310 helices.