Histidine decarboxylase

Source: Wikipedia, the free encyclopedia.
Histidine Decarboxylase
decarboxylases.[3][4] Eukaryotes, as well as gram-negative bacteria share a common HDC, while gram-positive bacteria employ an evolutionarily unrelated pyruvoyl-dependent HDC.[5] In humans, histidine decarboxylase is encoded by the HDC gene.[2][6]

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 histidine methyl ester, which was necessary for crystallization.[7] Generated from 4E1O.

Histidine decarboxylase is a

kDa polypeptide which is not enzymatically functional.[7][8] 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

vicinity of the active site lysine 305.[10]

Mechanism

aldimine with PLP. Then, histidine's carboxyl group leaves the substrate, forming carbon dioxide. This is the rate-limiting step of the all process, requiring an activation energy of 17.6 kcal/mol [12]
and fitting the experimental turnover of 1.73 .[13] After the decarboxylation takes place, the PLP intermediate is protonated by tyrosine 334 from the second subunit. The protonation is mediated by a water molecule and it is very fast and also very exergonic.[12] 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.[14] HDC is highly specific for its histidine substrate.[15]

Biological relevance

Histidine decarboxylase is the primary

smooth muscle relaxation.[18][19] H3 controls histamine turnover by feedback inhibition of histamine synthesis and release.[20] Finally, H4 plays roles in mast cell chemotaxis and cytokine production.[17]

In humans, HDC is primarily expressed in mast cells and basophil granulocytes. Accordingly, these cells contain the body's highest concentrations of histamine granules. Non-mast cell histamine is also found in the brain, where it is used as a neurotransmitter.[21]

Inhibition

HDC can be

α-fluoromethylhistidine and histidine methyl ester.[22][23]

Clinical significance

anti-tumoral, and anti-angiogenic effects.[25]

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.[26]

See also

References

  1. PMID 16747851
    .
  2. ^ a b "Entrez Gene: histidine decarboxylase".
  3. PMID 5681461
    .
  4. PMID 5216347
    .
  5. PMID 19302297
    .
  6. S2CID 23444983
    .
  7. ^
    PMID 22767596
    .
  8. ^ 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.
  9. S2CID 9206252
    .
  10. PMID 8181483
    .
  11. ^
    S2CID 39078427
    .
  12. ^
    PMID 28613002
    .
  13. PMID 22767596
    .
  14. ^ "Pyridoxal phosphate-dependent decarboxylase". InterPro.
  15. PMID 15581583
    .
  16. PMID 20085595
    .
  17. ^
    PMID 26084539
    .
  18. PMID 23268457
    .
  19. ^ Hill, S.J. (1997). "Classification of Histamine Receptors". Pharmacological Reviews. 49: 253–278 – via ASPET.
  20. PMID 2172771
    .
  21. PMID 22586376
    .
  22. PMID 4032273
    .
  23. PMID 963031
    .
  24. ^ "Diphenhydramine Hydrochloride". Drugs.com.
  25. S2CID 24835261
    .
  26. ^ "Online Mendelian Inheritance in Man: histidine decarboxylase".

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Histidine_decarboxylase&oldid=1215636261"