Histidine decarboxylase

Histidine Decarboxylase

Cartoon depiction of C-truncated HDC dimer with PLP residing in active site.
Identifiers
EC number 4.1.1.22
CAS number 9024-61-7
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Histidine decarboxylase (HDC) is an enzyme responsible for catalyzing the decarboxylation of histidine to form histamine. In mammals, histamine is an important biogenic amine with regulatory roles in neurotransmission, gastric acid secretion and immune response.[1][2] Histidine decarboxylase is the sole member of the histamine synthesis pathway, producing histamine in a one-step reaction. Histamine cannot be generated by any other known enzyme.[3] HDC is therefore the primary source of histamine in most mammals and eukaryotes. The enzyme employs a pyridoxal 5'-phosphate (PLP) cofactor, in similarity to many amino acid decarboxylases.[4][5] Eukaryotes, as well as gram-negative bacteria share a common HDC, while gram-positive bacteria employ an evolutionarily unrelated pyruvoyl-dependent HDC.[6] In humans, histidine decarboxylase is encoded by the HDC gene.[2][7]

Structure

PLP is normally covalently bound to HDC at lysine 305. It is also held in place with hydrogen bonds to other nearby amino acids. Here, the active site is shown with PLP bound to an inhibitory methyl-ester histidine residue, which was necessary for crystallization.[8] Generated from 4E1O.

Histidine decarboxylase is a group II pyridoxal-dependent decarboxylase, along with aromatic-L-amino-acid decarboxylase, and tyrosine decarboxylase. HDC is expressed as a 74 kDa polypeptide which is not enzymatically functional.[8][9] Only after post-translational processing does the enzyme become active. This processing consists of truncating much of the protein's C-terminal chain, reducing the peptide molecular weight to 54 kDa.

Histidine decarboxylase exists as a homodimer, with several amino acids from the respective opposing chain stabilizing the HDC active site. In HDC's resting state, PLP is covalently bound in a Schiff base to lysine 305, and stabilized by several hydrogen bonds to nearby amino acids aspartate 273, serine 151 and the opposing chain's serine 354.[8] HDC contains several regions that are sequentially and structurally similar to those in a number of other pyridoxal-dependent decarboxylases.[10] This is particularly evident in the vicinity of the active site lysine 305.[11]

Mechanism

Mechanism of histidine decarboxylation by HDC using the PLP co-factor.[12] This mechanism is similar to many other PLP-dependent carboxylases.

HDC decarboxylates histidine through the use of a PLP cofactor initially bound in a Schiff base to lysine 305.[12] Histidine initiates the reaction by displacing lysine 305 and forming a aldimine with PLP. Histidine's carboxyl group then leaves, forming carbon dioxide. Finally, PLP re-forms its original Schiff base at lysine 305, and histamine is released. This mechanism is very similar to those employed by other pyridoxal-dependent decarboxylases. In particular, the aldimine intermediate is a common feature of all known PLP-dependent decarboxylases.[13] HDC is highly specific for its histidine substrate.[14]

Biological Relevance

Histidine decarboxylase is the primary biological source of histamine. Histamine is an important biogenic amine that moderates numerous physiologic processes. There are four different histamine receptors, H1, H2, H3, and H4,[3] each of which carries a different biological significance. H1 modulates several functions of the central and peripheral nervous system, including circadian rhythm, body temperature and appetite.[15] H2 activation results in gastric acid secretion and smooth muscle relaxation.[16][17] H3 controls histamine turnover by feedback inhibition of histamine synthesis and release.[18] Finally, H4 plays roles in mast cell chemotaxis and cytokine production.[15]

In humans, HDC is primarily expressed in mast cells and basophil granulocytes. Accordingly, these cells contain the body's highest concentrations of histamine granules. No-mast cell histamine is also found in the brain, where it is used as a neurotransmitter.[19]

Clinical Significance

Antihistamines are a class of medications designed to reduce unwanted effects of histamine in the body. Typical antihistamines block specific histamine receptors, depending on what physiological purpose they serve. For example, diphenhydramine (Benadryl™), targets and inhibits the H1 histamine receptor to relieve symptoms of allergic reactions.[20] Inhibitors of histidine decarboxylase can conceivably be used as atypical antihistamines. Tritoqualine, as well as various catechins, such as epigallocatechin-3-gallate, a major component of green tea, have been shown to target HDC and histamine-producing cells, reducing histamine levels and providing anti-inflammatory, anti-tumoral, and anti-angiogenic effects.[21]

Mutations in the gene for Histidine decarboxylase have been observed in one family with Tourette syndrome (TS) and are not thought to account for most cases of TS.[22]

See also

References

  1. ↑ Epps HM (1945). "Studies on bacterial amino-acid decarboxylases: 4. l(-)-histidine decarboxylase from Cl. welchii Type A". Biochem. J. 39 (1): 42–6. PMC 1258146 Freely accessible. PMID 16747851.
  2. 1 2 "Entrez Gene: histidine decarboxylase".
  3. 1 2 Shahid, Mohammad (2009). "Histamine, Histamine Receptors, and their Role in Immunomodulation: An Updated Systematic Review" (PDF). The Open Immunology Journal. 2: 9–41.
  4. ↑ Riley WD, Snell EE (October 1968). "Histidine decarboxylase of Lactobacillus 30a. IV. The presence of covalently bound pyruvate as the prosthetic group". Biochemistry. 7 (10): 3520–8. PMID 5681461. doi:10.1021/bi00850a029.
  5. ↑ Rosenthaler J, Guirard BM, Chang GW, Snell EE (July 1965). "Purification and properties of histidine decarboxylase from Lactobacillus 30a". Proc. Natl. Acad. Sci. U.S.A. 54 (1): 152–8. PMC 285813 Freely accessible. PMID 5216347. doi:10.1073/pnas.54.1.152.
  6. ↑ Kimura, B.; Takahashi, H.; Hokimoto, S.; Tanaka, Y.; Fujii, T. (2009-08-01). "Induction of the histidine decarboxylase genes of Photobacterium damselae subsp. damselae (formally P. histaminum) at low pH". Journal of Applied Microbiology. 107 (2): 485–497. ISSN 1365-2672. doi:10.1111/j.1365-2672.2009.04223.x.
  7. ↑ Bruneau G, Nguyen VC, Gros F, Bernheim A, Thibault J (November 1992). "Preparation of a rat brain histidine decarboxylase (HDC) cDNA probe by PCR and assignment of the human HDC gene to chromosome 15". Hum. Genet. 90 (3): 235–8. PMID 1487235. doi:10.1007/bf00220068.
  8. 1 2 3 Komori, Hirofumi; Nitta, Yoko; Ueno, Hiroshi; Higuchi, Yoshiki (2012-08-17). "Structural Study Reveals That Ser-354 Determines Substrate Specificity on Human Histidine Decarboxylase". Journal of Biological Chemistry. 287 (34): 29175–29183. ISSN 0021-9258. PMC 3436558 Freely accessible. PMID 22767596. doi:10.1074/jbc.M112.381897.
  9. ↑ Nitta, Yoko (2010). "Expression of recombinant human histidine decarboxylase with full length and C-terminal truncated forms in yeast and bacterial cells" (PDF). J. Biol. Macromol. 10.
  10. ↑ Jackson, F. Rob (1990-10-01). "Prokaryotic and eukaryotic pyridoxal-dependent decarboxylases are homologous". Journal of Molecular Evolution. 31 (4): 325–329. ISSN 0022-2844. doi:10.1007/BF02101126.
  11. ↑ Sandmeier, Erika; Hale, Terence I.; Christen, Philipp (1994-05-01). "Multiple evolutionary origin of pyridoxal-5′-phosphate-dependent amino acid decarboxylases". European Journal of Biochemistry. 221 (3): 997–1002. ISSN 1432-1033. doi:10.1111/j.1432-1033.1994.tb18816.x.
  12. 1 2 Wu, Fang; Yu, Jing; Gehring, Heinz (2008-03-01). "Inhibitory and structural studies of novel coenzyme-substrate analogs of human histidine decarboxylase". The FASEB Journal. 22 (3): 890–897. ISSN 0892-6638. PMID 17965265. doi:10.1096/fj.07-9566com.
  13. ↑ "Pyridoxal phosphate-dependent decarboxylase". InterPro.
  14. ↑ Toney, Michael D. (2005-01-01). "Reaction specificity in pyridoxal phosphate enzymes". Archives of Biochemistry and Biophysics. Highlight issue on Enzyme Mechanisms. 433 (1): 279–287. doi:10.1016/j.abb.2004.09.037.
  15. 1 2 Panula, Pertti; Chazot, Paul L.; Cowart, Marlon; Gutzmer, Ralf; Leurs, Rob; Liu, Wai L. S.; Stark, Holger; Thurmond, Robin L.; Haas, Helmut L. (2015-07-01). "International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors". Pharmacological Reviews. 67 (3): 601–655. ISSN 1521-0081. PMC 4485016 Freely accessible. PMID 26084539. doi:10.1124/pr.114.010249.
  16. ↑ Canonica, G. Walter; Blaiss, Michael (2011-02-23). "Antihistaminic, Anti-Inflammatory, and Antiallergic Properties of the Nonsedating Second-Generation Antihistamine Desloratadine: a Review of the Evidence". World Allergy Organization Journal. 4 (2): 47. ISSN 1939-4551. PMC 3500039 Freely accessible. PMID 23268457. doi:10.1097/WOX.0b013e3182093e19.
  17. ↑ Hill, S.J. (1997). "Classification of Histamine Receptors". Pharmacological Reviews. 49: 253–278 – via ASPET.
  18. ↑ West, R. E.; Zweig, A.; Shih, N. Y.; Siegel, M. I.; Egan, R. W.; Clark, M. A. (1990-11-01). "Identification of two H3-histamine receptor subtypes". Molecular Pharmacology. 38 (5): 610–613. ISSN 0026-895X. PMID 2172771.
  19. ↑ Blandina, Patrizio; Provensi, Gustavo; Munari, Leonardo; Passani, Maria Beatrice (2012-01-01). "Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations?". Frontiers in Systems Neuroscience. 6. ISSN 1662-5137. PMC 3343474 Freely accessible. PMID 22586376. doi:10.3389/fnsys.2012.00033.
  20. ↑ "Diphenhydramine Hydrochloride". Drugs.com.
  21. ↑ Melgarejo, Esther; Medina, Miguel Ángel; Sánchez-Jiménez, Francisca; Urdiales, José Luis (2010-09-01). "Targeting of histamine producing cells by EGCG: a green dart against inflammation?". Journal of Physiology and Biochemistry. 66 (3): 265–270. ISSN 1138-7548. doi:10.1007/s13105-010-0033-7.
  22. ↑ "Online Mendelian Inheritance in Man: histidine decarboxylase".

Further reading

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