| General Information |
| MoonProt ID | 128 |
| First appeared in release | 1.0 |
| Name(s) | Leukotriene A-4 hydrolase
LTA-4 hydrolase
LTA4
Leukotriene A(4) hydrolase
Gene Name:LTA4H
|
| UniProt ID | P09960 (LKHA4_HUMAN) Reviewed |
| GO terms | GO: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 |
| Organisms for which functions have been demonstrated | Homo sapiens (human, a mammal) |
| Sequence length | 611 |
| FASTA sequence | >gi|4505029|ref|NP_000886.1| leukotriene A-4 hydrolase isoform 1 [Homo sapiens]
MPEIVDTCSLASPASVCRTKHLHLRCSVDFTRRTLTGTAALTVQSQEDNLRSLVLDTKDLTIEKVVINGQEVKYALGERQSYKGSPMEISLPIALSKNQEIVIEISFETSPKSSALQWLTPEQTSGKEHPYLFSQCQAIHCRAILPCQDTPSVKLTYTAEVSVPKELVALMSAIRDGETPDPEDPSRKIYKFIQKVPIPCYLIALVVGALESRQIGPRTLVWSEKEQVEKSAYEFSETESMLKIAEDLGGPYVWGQYDLLVLPPSFPYGGMENPCLTFVTPTLLAGDKSLSNVIAHEISHSWTGNLVTNKTWDHFWLNEGHTVYLERHICGRLFGEKFRHFNALGGWGELQNSVKTFGETHPFTKLVVDLTDIDPDVAYSSVPYEKGFALLFYLEQLLGGPEIFLGFLKAYVEKFSYKSITTDDWKDFLYSYFKDKVDVLNQVDWNAWLYSPGLPPIKPNYDMTLTNACIALSQRWITAKEDDLNSFNATDLKDLSSHQLNEFLAQTLQRAPLPLGHIKRMQEVYNFNAINNSEIRFRWLRLCIQSKWEDAIPLALKMATEQGRMKFTRPLFKDLAAFDKSHDQAVRTYQEHKASMHPVTAMLVGKDLKVD
|
| Structure Information |
| PDB ID | 1HS6,
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 | |
| SCOP | Zincin-like, alpha-alpha superhelix, Zn aminopeptidase N-terminal domain, |
| CATH | 2.60.40.1730, 3.30.2010.30, 1.10.390.10, 1.25.40.320 |
| TM Helix Prediction | no TM helices |
| DisProt Annotation | Not in DisProt |
| Predicted Disorder Regions | 1-10, 176-186, 352-362, 482-485, 609-611 |
| Connections to Disease |
| OMIM ID | |
| Function 1 |
| Function description | Leukotriene 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 function | Thunnissen 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. number | 3.3.2.6 |
| Location of functional site(s) | |
| Cellular location of function | cytosol |
| Comments | Glu-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 description | Aminopeptidase, enzyme |
| References for function | Rudberg 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. number | 3.4.11.24 |
| Location of functional site(s) | |
| Cellular location of function | cytosol |
| Comments | functional 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 |