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Title:Head-to-head terpene synthases: Mechanism of action and inhibition
Author(s):Lin, Fu-Yang
Director of Research:Oldfield, Eric
Doctoral Committee Chair(s):Oldfield, Eric
Doctoral Committee Member(s):Gennis, Robert B.; Nair, Satish K.; Mitchell, Douglas A.
Department / Program:School of Molecular & Cell Bio
Discipline:Biophysics & Computnl Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
virulence factor
dehydrosqualene synthase
Dehydrosqualene synthase (CrtM)
squalene synthase (SQS)
drug design
high throughput screening
Abstract:“Head-to-head” terpene synthases catalyze the first committed steps in sterol and carotenoid biosynthesis: the condensation of two isoprenoid diphosphates to form cyclopropylcarbinyl diphosphates, followed by ring opening. In this work, I used x-ray crystallography, and mutagenesis to study the catalytic mechanism of Staphylococcus aureus dehydrosqualene synthase. Dehydrosqualene synthase (CrtM) is also the first committed enzyme in the biosynthesis of staphyloxanthin, a carotenoid pigment, and a major virulence factor in S. aureus. Inhibitors targeting CrtM and staphyloxanthin biosynthesis are therefore of interest as “anti-virulence” based therapy for treating S. aureus infection. I studied the structure-activity-relationship of phosphonosulfonate and phosphonoacetamide compounds in CrtM inhibition, and I also developed a series of non-phosphonate CrtM inhibitors using rational- and structure-based approaches.
Issue Date:2011-05-25
Rights Information:Copyright 2011 Fu-Yang Lin
Date Available in IDEALS:2011-05-25
Date Deposited:2011-05

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