Abstract:
The leukotriene A4 hydrolase (LTA4H) protein is a zinc-containing bifunctional
enzyme with epoxide hydrolase (EH) activity and aminopeptidase (AP) activity. LTA4H
has long been regarded as an anti-inflammatory target since it controls the rate-limiting
step in the biosynthesis of the inflammatory mediator leukotriene B4 (LTB4). In addition
to the EH activity, LTA4H is an aminopeptidase which has a broad substrates specificity.
It is proposed that the LTA4H aminopeptidase activity may have an important role in the
processing of peptides related to inflammation. The small molecule 4-
methoxydiphenylmethane (4MDM) was reported previously to selectively augment the
LTA4H aminopeptidase activity without affecting the bioproduction of LTB4 in vivo.
Thus, this thesis aims to determine the mechanism of LTA4H-mediated hydrolysis of
peptidyl substrates in the presence of 4MDM.
