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This Sandbox is Reserved from Sep 25, 2013, through Mar 31, 2014 for use in the course "BCH455/555 Proteins and Molecular Mechanisms" taught by Michael B. Goshe at the North Carolina State University. This reservation includes Sandbox Reserved 299, Sandbox Reserved 300 and Sandbox Reserved 760 through Sandbox Reserved 779.
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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]

Asymmetrical unit of Histidine Decarboxylase bound to 3 substrate analogs Histidine methyl ester (HME)

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Contents


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

Figure 2. Sequence of Histidine Decarboxylase with its corresponding secondary stuctures
Figure 2. Sequence of Histidine Decarboxylase with its corresponding secondary stuctures [4]

Histidine Decarboxylase is considered to be a homo-dimer when one observe its biological assembly. A homo-dimer is a quaternary structure formed by two identical monomers or protein chains. In human, three human HDC (hHDC) homo-dimers can be joined together to form a trimer asymmetric unit [6] [8]. 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 [8].

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) [6]. A monomer is also composed of 49% helical structure and 13% beta sheet [4]. One specifically long α-helix which span from Valine-359 to Arginine-393 connects the large and small domains together (Figure 2). Through hydrophobic effect, the N-terminal regions of the two monomers interact with each other extensively. At the same time, the large domains interact extensively due to electrostatic interactions. Thus, the N-terminal regions and large domains form the dimer interfaces of HDC [6].


Cofactor and Substrate Binding Pocket

References

  1. ↑ Taguchi Y, Watanabe T, Kubota H, Hayashi H, Wada H. Purification of histidine decarboxylase from the liver of fetal rats and its immunochemical and immunohistochemical characterization. J Biol Chem. 1984 Apr 25;259(8):5214-21. PMID:6425286
  2. ↑ 2.0 2.1 2.2 Ohmori E, Fukui T, Imanishi N, Yatsunami K, Ichikawa A. Purification and characterization of l-histidine decarboxylase from mouse mastocytoma P-815 cells. J Biochem. 1990 Jun;107(6):834-9. PMID:2118138
  3. ↑ Schwelberger, Hubert G. "Metabolism of Histamine." European Histamine Research Society Nov. 2013. Web. 29 Nov. 2013. http://www.ehrs.org.uk/schwelberger.pdf
  4. ↑ 4.0 4.1 4.2 4.3 4.4 "Human Histidine Decarboxylase Complex with Histidine Methyl Ester (HME)." RSCB Protein Data Bank. RCSB. Web. 29 Nov. 2013. <http://www.rcsb.org/pdb/explore/explore.do?structureId=4E1O>.
  5. ↑ 5.0 5.1 Watabe A, Fukui T, Ohmori E, Ichikawa A. Purification and properties of L-histidine decarboxylase from mouse stomach. Biochem Pharmacol. 1992 Feb 4;43(3):587-93. PMID:1540215
  6. ↑ 6.0 6.1 6.2 6.3 Komori H, Nitta Y, Ueno H, Higuchi Y. Structural study reveals Ser345 determines substrate specificity on human histidine decarboxylase. J Biol Chem. 2012 Jul 5. PMID:22767596 doi:10.1074/jbc.M112.381897
  7. ↑ "P19113 (DCHS_HUMAN)." UniProt. Protein Knowledgebase. Web. 29 Nov. 2013 <http://www.uniprot.org/uniprot/P19113>.
  8. ↑ 8.0 8.1 Komori H, Nitta Y, Ueno H, Higuchi Y. Purification, crystallization and preliminary X-ray analysis of human histidine decarboxylase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Jun 1;68(Pt 6):675-7. doi:, 10.1107/S1744309112015692. Epub 2012 May 23. PMID:22684068 doi:http://dx.doi.org/10.1107/S1744309112015692
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