Leukotriene-A4 hydrolase explained

leukotriene-A4 hydrolase
Ec Number:3.3.2.6
Cas Number:90119-07-6
Go Code:0004463
leukotriene A4 hydrolase
Caption:Crystallographic structure of LTA4H (rainbow colored N-terminus = blue, C-terminus = red) complexed with the protease inhibitor bestatin (space-filling model, carbon = white, oxygen = red, nitrogen = blue) based on the structure.
Width:325px
Hgncid:6710
Symbol:LTA4H
Entrezgene:4048
Omim:151570
Refseq:NM_000895
Uniprot:P09960
Pdb:1SQM
Ecnumber:3.3.2.6
Chromosome:12
Arm:q
Band:22

Leukotriene-A4 hydrolase is an enzyme that catalyzes the reaction which converts Leukotriene A4 to Leukotriene B4.[1] It is a bifunctional zinc enzyme (EC 3.3.2.6) with different amino acids attached to it to aid in the catalysis of the reaction. It also acts as an aminopeptidase. Leukotriene-A4 hydrolase is a cytosolic protein and is found in almost all mammalian cells, tissues and organelles that have been examined.

Function

This enzyme belongs to the family of hydrolases, specifically those acting on ether bonds (ether hydrolases). The systematic name of this enzyme class is (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase. Other names in common use include LTA4 hydrolase, LTA4H, and leukotriene A4 hydrolase. This enzyme participates in arachidonic acid metabolism.

Catalyzed reaction

Leukotriene A4 Hydrolase catalyzes the reaction which converts leukotriene A4 to leukotriene B4. The Leukotriene A4 structure contains an epoxide ring functional group, which are highly reactive due to its ring strain making them extremely electrophilic. This drives the reaction forward, favouring the products Leukotriene B4. Leukotriene A4 hydrolase adds a water molecule across the epoxide ring on Leukotriene A4. The addition of the water molecule opens the epoxide ring and causes the formation of the Hydroxy group at the carbon attached to the oxygen from the epoxide. The second carbon involved in the epoxide ring remains the same resulting in leukotriene B4. The water molecule attacking the double bond also forms into a hydroxy group after work-up. The product of the reaction is Leukotriene B4. ----

Structure

As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes,,, and .

Further reading

Notes and References

  1. Web site: Leukotriene-A4 Hydrolase - an overview ScienceDirect Topics . 2024-04-14 . www.sciencedirect.com.