The long-term objectives of this research are to establish the detailed nature of the biochemical processes involved in phenylpropanoid metabolism, which together constitutes approximately 30% of the carbon in vascular plants. This includes the enzymes and protein factors involved in biochemical pathways to the medicinally important lignans and isoflavonoids, as well as to the structural plant polymeric lignins. Of these the lignans and isoflavonoids have important roles in human health protection (e.g., chemoprotection against various cancers, in lowering blood cholesterol levels) in treatment of various cancers (e.g., testicular), and in prevention of certain allergies.This particular proposal aims to define the mode of action of the first known protein able to control the binding and orientation of plant phenols (monolignol derived) in order that stereoselective coupling can occur. It is considered that definition of the functional motifs on this protein will aid greatly in identification of other analogous proteins of similar function. Additionally, we wish to examine three aromatic alcohol dehydrogenases involved in key steps to these medicinally important lignans and isoflavonoids, in order to determine how differing enantiospecificity is achieved albeit in each case all going through similar enone intermediates. The primary emphasis of the study will thus employ x-ray crystallographic analysis of each protein with substrates, substrate analogs and inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM066173-04
Application #
6918038
Study Section
Physical Biochemistry Study Section (PB)
Program Officer
Flicker, Paula F
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2005
Total Cost
$216,333
Indirect Cost
Name
Washington State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
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Youn, Buhyun; Sellhorn, George E; Mirchel, Ryan J et al. (2006) Crystal structures of vegetative soybean lipoxygenase VLX-B and VLX-D, and comparisons with seed isoforms LOX-1 and LOX-3. Proteins 65:1008-20
Davin, Laurence B; Lewis, Norman G (2005) Dirigent phenoxy radical coupling: advances and challenges. Curr Opin Biotechnol 16:398-406
Park, Il Yeong; Youn, Buhyun; Harley, Jill L et al. (2004) The unique hydrogen bonded water in the reduced form of Clostridium pasteurianum rubredoxin and its possible role in electron transfer. J Biol Inorg Chem 9:423-8

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