Members of this family represent a distinctive subset within the zinc metallopeptidases of MEROPS peptidase family M1 (aminopeptidase N, clan MA). This entry represents leukotriene A-4 hydrolase (LTA4), which in vertebrates has both epoxide hydrolase and aminopeptidase activity at the same active site []. In contrast, highly homologous enzymes from yeast only have the aminopeptidase activity, showing low epoxide hydrolase activity in vitro. This is the case for leucine aminopeptidase LTA4H from budding yeast [].
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 []. The two activities occupy different, but overlapping sites [, ]. The activity and physiological relevance of the aminopeptidase is as yet unknown while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), apotent chemotaxin that is fundamental to the inflammatory response of mammals [, ]. 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 []. 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 [].
