Leukotriene-A4 hydrolase
{{infobox enzyme
| Name = leukotriene-A4 hydrolase
| EC_number = 3.3.2.6
| CAS_number = 90119-07-6
| GO_code = 0004463
| image =
| width =
| caption =
}}
{{infobox protein
|Name=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 {{PDB|1HS6}} structure.
|image= 1HS6.png
|width=325px
|HGNCid=6710
|Symbol=LTA4H
|AltSymbols=
|EntrezGene=4048
|OMIM=151570
|RefSeq=NM_000895
|UniProt=P09960
|PDB=1SQM
|ECnumber=3.3.2.6
|Chromosome=12
|Arm=q
|Band=22
|LocusSupplementaryData=
}}
Leukotriene-A4 hydrolase is an enzyme that catalyzes the reaction which converts Leukotriene A4 to Leukotriene B4.{{Cite web |title=Leukotriene-A4 Hydrolase - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/leukotriene-a4-hydrolase#:~:text=Leukotriene%20A4%20(LTA)%20hydrolase,the%20product%20of%205-lipoxygenase. |access-date=2024-04-14 |website=www.sciencedirect.com}}
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
Image:LTA4H rxn.svgLeukotriene 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.
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Structure
As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes {{PDB link|1GW6}}, {{PDB link|1H19}}, {{PDB link|1HS6}}, and {{PDB link|1SQM}}.
References
{{Reflist|2}}
Further reading
{{refbegin | 2}}
- {{cite journal | vauthors = Evans JF, Dupuis P, Ford-Hutchinson AW | date = 1985 | title = Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils | journal = Biochim. Biophys. Acta | volume = 840 | pages = 43–50 | pmid = 3995081 | issue = 1 | doi=10.1016/0304-4165(85)90160-6}}
- {{cite journal | vauthors = Shimizu T, Seyama Y, Suzuki K | date = 1987 | title = Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis | journal = J. Biol. Chem. | volume = 262 | pages = 13873–6 | pmid = 3654641 | issue = 29 | doi = 10.1016/S0021-9258(18)47872-6 | doi-access = free }}
- {{cite journal | vauthors = Haeggstrom J, Meijer J, Radmark O | date = 1986 | title = Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase | journal = J. Biol. Chem. | volume = 261 | pages = 6332–7 | pmid = 3009453 | issue = 14 | doi = 10.1016/S0021-9258(19)84567-2 | doi-access = free }}
- {{cite journal | vauthors = Newman JW, Morisseau C, Hammock BD | date = 2005 | title = Epoxide hydrolases: their roles and interactions with lipid metabolism | journal = Prog. Lipid Res. | volume = 44 | pages = 1–51 | pmid = 15748653 | doi = 10.1016/j.plipres.2004.10.001 | issue = 1 }}
- {{cite journal | vauthors = Fretland AJ, Omiecinski CJ | date = 2000 | title = Epoxide hydrolases: biochemistry and molecular biology | journal = Chem. Biol. Interact. | volume = 129 | pages = 41–59 | pmid = 11154734 | doi = 10.1016/S0009-2797(00)00197-6 | issue = 1–2 | bibcode = 2000CBI...129...41F | citeseerx = 10.1.1.462.3157 | url = http://www.personal.psu.edu/faculty/c/j/cjo10/PDFs/FretlandEHRev-2000.pdf }}
- {{cite journal | vauthors = Orning L, Gierse JK, Fitzpatrick FA | date = 1994 | title = The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity | journal = J. Biol. Chem. | volume = 269 | pages = 11269–73 | pmid = 8157657 | issue = 15 | doi = 10.1016/S0021-9258(19)78120-4 | doi-access = free }}
- {{cite journal | vauthors = Ohishi N, Izumi T, Minami M, Kitamura S, Seyama Y, Ohkawa S, Terao S, Yotsumoto H, Takaku F, Shimizu T | date = 1987 | title = Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers | journal = J. Biol. Chem. | volume = 262 | pages = 10200–5 | pmid = 3038871 | issue = 21 | doi = 10.1016/S0021-9258(18)61098-1 | doi-access = free }}
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External links
- {{MeshName|leukotriene+A4+hydrolase|3=leukotriene A4 hydrolase}}
{{Metabolism of complex lipids}}
{{Leukotrienergics}}
{{Ether bond hydrolases}}
{{Enzymes}}
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Category:Enzymes of known structure
{{hydrolase-stub}}