InterPro domain: IPR034015

This entry includes leukotriene A4 hydrolase (LTA4H; E.C. 3.3.2.6; MEROPS identifier M01.004) and the close homologues cold-active aminopeptidase ( Colwellia psychrerythraea -type peptidase; ColAP; MEROPS identifier M01.031), and arginyl aminopeptidase-like 1 (also known as aminopeptidase RNPEPL1, MEROPS identifier M01.022), all members of the aminopeptidase M1 family. LTA4H, is a bifunctional enzyme possessing an aminopeptidase as well as an epoxide hydrolase activity [ 1 ]. The two activities occupy different, but overlapping sites [ 2 , 3 ]. The activity and physiological relevance of the aminopeptidase is as yet unknown while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals [ 4 , 5 ]. It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives. The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase [ 6 ]. LTA4H is overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well known red wine polyphenolic compound with cancer chemopreventive activity [ 7 ].

1. Structure and catalytic mechanisms of leukotriene A4 hydrolase. Prostaglandins Other Lipid Mediat. 83, 198-202
2. Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms. J. Biol. Chem. 277, 1398-404
3. Crystal structure of leukotriene A4 hydrolase in complex with kelatorphan, implications for design of zinc metallopeptidase inhibitors. FEBS Lett. 584, 3446-51
4. Structures and mechanisms of enzymes in the leukotriene cascade. Biochimie 92, 676-81
5. Leukotriene A(4) hydrolase inhibition attenuates allergic airway inflammation and hyperresponsiveness. Am. J. Respir. Crit. Care Med. 181, 899-907
6. Modulating the substrate specificity of LTA4H aminopeptidase by using chemical compounds and small-molecule-guided mutagenesis. Chembiochem 11, 1120-8
7. Resveratrol, a red wine polyphenol, suppresses pancreatic cancer by inhibiting leukotriene Aâ‚„hydrolase. Cancer Res. 70, 9755-64