THE IMPACT OF GLYCOSYLATION ON ACTIVE SITE STRUCTURE AND ACTIVITY IN THE FUNGUS ENZYME MOLOX

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Anastasiia Kostenko (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Lipoxygenases from pathogenic fungi belong to the lipoxygenase family that catalyze the C-H activation of polyunsaturated fatty acids to form diverse hydroperoxides. While the lipoxygenase catalytic domains are structurally and functionally similar , the fungal enzymes are decorated with N-linked glycosylations. MoLOX , a lipoxygenase from the fungus M. oryzae , is emerging as an important target for the devastating rice blast disease. Here we demonstrate for the first time that hydrogen transfer , associated with C-H cleavage of linoleic acid by MoLOX , occurs by a hydrogen tunneling mechanism. Using the temperature dependent kinetic isotope effect , [delta]Ea , as a kinetic reporter of tunneling efficiency , the loss of N-linked carbohydrates is linked to an increase in the activation energy for deuterium transfer , consistent with an impairment of the tunneling ready state. These results have important implications for MoLOX inhibitor design towards a potential 'treatment' of rice blast disease.

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Thesis

Language: English

Date: 2019

Keywords

C-H activation

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