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Histidine Decarboxylase

Histidine Decarboxylase (HDC) is an enzyme that is responsible for converting histamine from amino acid L-histidine. This enzyme belongs in the group II pyridoxal-5-phosphate (PLP)-dependent decarboxylase family. As the name suggested, this enzyme catalyzes the production of histamine by the removal of carboxylate group from the amino acid L-histidine whilst utilize pyridoxal phosphate as a cofactor. The mammalian Histamine decarboxylase is originated from HDC gene which encodes a 74kDa precursor polypeptide. However, the enzyme becomes active when its C-terminal is truncated into 54kDa during post-translation process. ^{[1] [2] [3]}

Contents 1 Histidine Decarboxylase 1.1 General Information 1.2 Sequence and Structure 1.3 Implication 1.4 References

spinqualitylabelsall models Asymmetrical unit of Histidine Decarboxylase bound to 3 substrate analogs Histidine methyl ester (HME) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

General Information

Histidine Decarboxylase

Symbol: HDC

Gene Name: HDC gene

Organism: Homo sapiens

Classification: Lyase

Length: 481 residues ^[4]

Chains: A, B, C, D, E, F ^[4]

Molecular Weight: 54314.8 kDa per chain ^[4]

Isoelectric Point: 5.4 (mouse HDC) ^{[5] [2]}

Km: 0.1 mM (human)^{[6] [7]}, 0.29mM (mouse stomach)^[5], 0.26mM (mouse mastocytoma P-815 cells) ^[2]

Vmax: 1880 nmol/min/mg

Sequence and Structure

Histidine Decarboxylase is considered to be a homo-dimer when one observe its biological assembly]link proteopedia). A homo-dimer is a quaternary structure (link) formed by, usually non-covalently bound, identical monomers or protein chains. In human, three human HDC (hHDC) homo-dimers can be joined together to form a trimer asymmetrical unit (link proteopedia) [jbc, 4e10]. Thus, one can use the nomenclature “trimer of dimer” to suggest the complex might dissociate into smaller subunits before dissociating into monomers. The asymmetrical unit can be seen in Figure 1. Specifically, Cystein-180 and Cystein-418 are primary responsible for the oligomerization process of HDC [22].

Each monomer is divided into 3 structural domains: N-terminal (2-71), large domain (71-371), and small domain (372-477) (green link/figure 5) [jbc].The monomer is also composed of 49% helical structure and 13% beta sheet as depicted in Figure 2 [4e10]. One specifically long α-helix which span from Valine-359 to Arginine-393 connects the large and small domains together. Through hydrophobic effect, the N-terminal regions of the two monomers interact with each other extensively [jbc]. At the same time, the large domains interact extensively due to electrostatic interactions [jbc]. Thus, the N-terminal regions and large domains form the dimer interfaces of HDC.

Implication

Histidine decarboxylase is responsible for the synthesis of histamine. Histamine is an important key factor for various physiological processes such as gastric acid secretion (3,4), immune response (1,2), cell growth (8-10), and neurotrasmission for appetite, memory, or circadian rhythm (5-7). As a result, any imbalance or distortion of the histamine metabolism can often contribute to a high probability for peptic ulcer, inflammation responses, schizophrenia, or tumor progression (5-7).

References