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oai:www.ideals.illinois.edu:2142/24489 2023-07-10 col_2142_5131 col_2142_14828 com_2142_5130 com_2142_14827 com_2142_14793 com_2142_8903

Oldfield, Eric Oldfield, Eric Gennis, Robert B. Nair, Satish K. Mitchell, Douglas A. Lin, Fu-Yang 2011-05-25T14:27:33Z 2011-05-25T14:27:33Z 2013-05-26T10:00:19Z 2011-05-25T14:27:33Z 2011-05 “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. Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2011-04-18T13:27:52Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 LIN_FUYANG.pdf: 37580860 bytes, checksum: 31b26dfcee81cdb98d598568899383a1 (MD5) Made available in DSpace on 2011-05-25T14:27:33Z (GMT). No. of bitstreams: 2 Lin_FuYang.pdf: 37586175 bytes, checksum: d864e3c2d8550403150e0f375dbf9746 (MD5) license.txt: 4053 bytes, checksum: 9fca916d201abc14ce7d6609623d7108 (MD5) Item marked as restricted to the 'Administrator' Group (id=1) by William Ingram (wingram2@illinois.edu) on 2011-05-25T14:30:00Z Item is restricted until 2013-05-25T14:29:35Z Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2013-05-26T10:00:19Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations - Biophysics and Computational Biology (ID: 689) No. of bitstreams: 3 Lin_FuYang.pdf.txt: 178329 bytes, checksum: 998cc686b73acebaaecc58d8055c1f28 (MD5) Lin_FuYang.pdf: 37586175 bytes, checksum: d864e3c2d8550403150e0f375dbf9746 (MD5) license.txt: 4053 bytes, checksum: 9fca916d201abc14ce7d6609623d7108 (MD5) Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2013-05-26T10:00:19Z http://hdl.handle.net/2142/24489 en Copyright 2011 Fu-Yang Lin terpenes isoprenoids antibiotics virulence factor dehydrosqualene synthase Dehydrosqualene synthase (CrtM) squalene synthase (SQS) drug design high throughput screening Head-to-head terpene synthases: Mechanism of action and inhibition School of Molecular & Cell Bio 1415 Biophysics & Computnl Biology 0319 University of Illinois at Urbana-Champaign Dissertation Ph.D. PHD:Biophys&Computnl Bio -UIUC 10KS0319PHD