Leukotriene A4 hydrolase , also known as LTA4H is a human gene .[1] [2] [3] The protein encoded by this gene is a bifunctional enzyme (EC 3.3.2.6 ) which converts leukotriene A4 to leukotriene B4 and acts as an aminopeptidase .[4]
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
The chemical reaction catalyzed by LTA4H.
Structure
As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes 1GW6 , 1H19 , 1HS6 , and 1SQM .
References
^ Minami M, Ohno S, Kawasaki H, Rådmark O, Samuelsson B, Jörnvall H, Shimizu T, Seyama Y, Suzuki K (October 1987). "Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis" . J. Biol. Chem . 262 (29): 13873–6. doi :10.1016/S0021-9258(18)47872-6 . PMID 3654641 . Archived from the original on 2005-03-30. Retrieved 2008-09-04 .
^ FFunk CD, Rådmark O, Fu JY, Matsumoto T, Jörnvall H, Shimizu T, Samuelsson B (October 1987). "Molecular cloning and amino acid sequence of leukotriene A4 hydrolase" . Proc. Natl. Acad. Sci. U.S.A . 84 (19): 6677–81. Bibcode :1987PNAS...84.6677F . doi :10.1073/pnas.84.19.6677 . PMC 299146 . PMID 2821541 .
^ Mancini JA, Evans JF (July 1995). "Cloning and characterization of the human leukotriene A4 hydrolase gene". Eur. J. Biochem . 231 (1): 65–71. doi :10.1111/j.1432-1033.1995.tb20671.x . PMID 7628486 .
^ Rudberg PC, Tholander F, Andberg M, Thunnissen MM, Haeggström JZ (June 2004). "Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates" . J. Biol. Chem . 279 (26): 27376–82. doi :10.1074/jbc.M401031200 . PMID 15078870 .
Further reading
Evans JF, Dupuis P, Ford-Hutchinson AW (1985). "Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils". Biochim. Biophys. Acta . 840 (1): 43–50. doi :10.1016/0304-4165(85)90160-6 . PMID 3995081 .
Shimizu T, Seyama Y, Suzuki K (1987). "Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis" . J. Biol. Chem . 262 (29): 13873–6. doi :10.1016/S0021-9258(18)47872-6 . PMID 3654641 .
Haeggstrom J, Meijer J, Radmark O (1986). "Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase" . J. Biol. Chem . 261 (14): 6332–7. doi :10.1016/S0021-9258(19)84567-2 . PMID 3009453 .
Newman JW, Morisseau C, Hammock BD (2005). "Epoxide hydrolases: their roles and interactions with lipid metabolism". Prog. Lipid Res . 44 (1): 1–51. doi :10.1016/j.plipres.2004.10.001 . PMID 15748653 .
Fretland AJ, Omiecinski CJ (2000). "Epoxide hydrolases: biochemistry and molecular biology" (PDF) . Chem. Biol. Interact . 129 (1–2): 41–59. CiteSeerX 10.1.1.462.3157 . doi :10.1016/S0009-2797(00)00197-6 . PMID 11154734 .
Orning L, Gierse JK, Fitzpatrick FA (1994). "The bifunctional enzyme leukotriene-A4 hydrolase is an arginine aminopeptidase of high efficiency and specificity" . J. Biol. Chem . 269 (15): 11269–73. doi :10.1016/S0021-9258(19)78120-4 . PMID 8157657 .
Ohishi N, Izumi T, Minami M, Kitamura S, Seyama Y, Ohkawa S, Terao S, Yotsumoto H, Takaku F, Shimizu T (1987). "Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers" . J. Biol. Chem . 262 (21): 10200–5. doi :10.1016/S0021-9258(18)61098-1 . PMID 3038871 .
External links
Receptor (ligands )
BLT Tooltip Leukotriene B4 receptor
BLT1 Tooltip Leukotriene B4 receptor 1 BLT2 Tooltip Leukotriene B4 receptor 2
CysLT Tooltip Cysteinyl leukotriene receptor
CysLT1 Tooltip Cysteinyl leukotriene receptor 1 CysLT2 Tooltip Cysteinyl leukotriene receptor 2 CysLTE Tooltip Cysteinyl leukotriene receptor E
Enzyme (inhibitors )
5-LOX Tooltip Arachidonate 5-lipoxygenase 12-LOX Tooltip Arachidonate 12-lipoxygenase 15-LOX Tooltip Arachidonate 15-lipoxygenase LTA4 H Tooltip Leukotriene A4 hydrolase LTB4 H Tooltip Leukotriene B4 ω-hydroxylase LTC4 S Tooltip Leukotriene C4 synthase LTC4 H Tooltip Leukotriene C4 hydrolase LTD4 Tooltip Leukotriene D4 hydrolase
Others
Activity Regulation Classification Kinetics Types