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Title page for ETD etd-02202012-105424


Type of Document Dissertation
Author Prage, Edward B
URN etd-02202012-105424
Title Structural Studies of Inhibition of the Human Inducible Prostaglandin E Synthase MPGES1
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Richard N Armstrong Committee Chair
Keywords
  • MAPEG
  • Eicosanoids
  • Inflammation
  • MPGES1
  • H/D Exchange
Date of Defense 2012-02-13
Availability unrestricted
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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