Protein Information

General Information
MoonProt ID128
First appeared in release1.0
Name(s)Leukotriene A-4 hydrolase LTA-4 hydrolase LTA4 Leukotriene A(4) hydrolase Gene Name:LTA4H
UniProt IDP09960 (LKHA4_HUMAN) Reviewed
GO termsGO:0006508 proteolysis GO:0006691 leukotriene metabolic process GO:0006954 inflammatory response GO:0019369 arachidonic acid metabolic process GO:0019370 leukotriene biosynthetic process GO:0043171 peptide catabolic process GO:0044281 small molecule metabolic process GO:0004177 aminopeptidase activity GO:0004301 epoxide hydrolase activity GO:0004463 leukotriene-A4 hydrolase activity GO:0008233 peptidase activity GO:0008237 metallopeptidase activity GO:0008270 zinc ion binding GO:0016787 hydrolase activity GO:0044822 poly(A) RNA binding GO:0046872 metal ion binding GO:0005634 nucleus GO:0005737 cytoplasm GO:0005829 cytosol GO:0070062 extracellular vesicular exosome GO:0005730 nucleolus GO:0008233 peptidase activity GO:0004177 aminopeptidase activity
Organisms for which functions have been demonstratedHomo sapiens (Human)
Sequence length611
FASTA sequence>gi|4505029|ref|NP_000886.1| leukotriene A-4 hydrolase isoform 1 [Homo sapiens] MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDLTIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLTPEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETPDPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETESMLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISHSWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGETHPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSITTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAKEDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWLRLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVTAMLVGKDLKVD
Structure Information
PDB ID1HS6, 2VJ8, 3FTS, 3FTU, 3FTV, 3FTX, 3FTW, 3FU0 3FU3, 3FU5, 3FU6, 3FUD, 3FUE, 3FUF, 3FUH, 3FUI, 3FUJ, 3FUK, 3FUM, 3FUN, 3FH5, 3FH7, 3FH8, 3FHE, 3FTZ, 3FUL, 1H19, 3CHO, 3CHP, 3CHQ, 3CHR, 3CHS, 1GW6, 2R59, 3B7R, 3B7L, 3B7U, 3B7X, 1SQM
Quaternary structure
Function 1
Function descriptionLeukotriene A-4 hydrolase, enzyme epoxide hydrolase (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H(2)O <=> (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate catalyzes the last step in the biosynthesis of leukotriene B4. Lipid metabolism, leukotriene B4 biosynthesis
References for functionThunnissen MM, Nordlund P, Haeggstr?m JZ. Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Nat Struct Biol. 2001 Feb. PMID: 11175901
E.C. number3.3.2.6
Location of functional site(s)Active site:384,297 Metal binding site:319,296,300 Other functional site:376,379
Cellular location of functioncytosol
CommentsGlu-271 and Gln-136 located in the active site Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy) phenoxy] methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis. Sandanayaka V, Mamat B, Mishra RK, Winger J, Krohn M, Zhou LM, Keyvan M, Enache L, Sullins D, Onua E, Zhang J, Halldorsdottir G, Sigthorsdottir H, Thorlaksdottir A, Sigthorsson G, Thorsteinnsdottir M, Davies DR, Stewart LJ, Zembower DE, Andresson T, Kiselyov AS, Singh J, Gurney ME. J Med Chem. 2010 Jan 28;53(2):573-85. doi: 10.1021/jm900838g. PMID: 19950900
Function 2
Function descriptionAminopeptidase, enzyme
References for functionRudberg PC, Tholander F, Thunnissen MM, Haeggstr?m JZ. Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms. J Biol Chem. 2002 Jan 11. PMID: 11675384
E.C. number3.4.11.24
Location of functional site(s)
Cellular location of functioncytosol
Commentsfunctional site with Glu-271 interaction Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates. Rudberg PC, Tholander F, Andberg M, Thunnissen MM, Haeggstrm JZ. J Biol Chem. 2004 Jun 25;279(26):27376-82. PMID: 15078870