Substrate Effect on LTA4H Aminopeptidase Activity in The Presence of 4MDM



Yassa, Jacklin

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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.


This thesis has been embargoed for 10 years and will not be available until May 2029 at the earliest.


Lys-pNA hydrolysis, LTA4H, Aminopeptidase activity, 4MDM, Kinetic assay