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Leukotriene-A4 hydrolase

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leukotriene-A4 hydrolase
Identifiers
EC no.3.3.2.6
CAS no.90119-07-6
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
leukotriene A4 hydrolase
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 PDB: 1HS6​ structure.
Identifiers
SymbolLTA4H
NCBI gene4048
HGNC6710
OMIM151570
PDB1SQM
RefSeqNM_000895
UniProtP09960
Other data
EC number3.3.2.6
LocusChr. 12 q22
Search for
StructuresSwiss-model
DomainsInterPro

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.[1]

Function

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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

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The chemical reaction catalyzed by LTA4H.

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

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As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes 1GW6, 1H19, 1HS6, and 1SQM.

References

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  1. ^ a b "Leukotriene-A4 Hydrolase - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-14.

Further reading

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