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    Structural Studies of Inhibition of the Human Inducible Prostaglandin E Synthase MPGES1

    Prage, Edward B
    : https://etd.library.vanderbilt.edu/etd-02202012-105424
    http://hdl.handle.net/1803/10593
    : 2012-02-21

    Abstract

    The inducible enzyme microsomal prostaglandin E synthase 1 (MPGES1) is a glutathione-dependent prostaglandin H2 isomerase that has been implicated in a variety of inflammatory diseases and several forms of cancer. While there are currently no available drugs that selectively inhibit its activity, MPGES1 represents a promising therapeutic target. The aim of the research described here is to analyze the structural implications of the interaction of MPGES1 with different types of inhibitors. The structural dynamics determination technique hydrogen/deuterium exchange mass spectrometry was utilized to locate spatially distinct inhibitor binding sites within the enzyme. The method was also used, coupled with biochemical techniques, to defined the modes of inhibition of MPGES1 by the cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2.
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