? Understanding how enzymes achieve their enormous catalytic power and exquisite specificity is central to the study of biological function. Over the past decades many basic features of enzyme function and behavior have been illuminated. Nevertheless, the extraordinary rate enhancements and specificites of enzymes cannot be accounted for quantitatively. Unnatural amino acids are required to probe at an unprecedented depth the energetic consequences of what is arguably the most profound difference between enzymatic and uncatalyzed solution reactions-carrying out reactions in the idiosyncratic and highly specialized enzyme active site instead of aqueous solution. A series of ketosteroid isomerase variants will be generated in which the properties of an active site aspartic acid residue (Asp 103) that donates a hydrogen bond are varied systematically and rationally. These studies will deepen our understanding of hydrogen bonding energetics within an enzyme active site and advance our understanding of the properties of the enzymatic environment that dictate the nature and energetics of such hydrogen bonds. These experiments will serve as a foundation for the use of systematic and incisive chemical perturbation in the study of enzymes. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM075693-01
Application #
6998026
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Marino, Pamela
Project Start
2006-01-01
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
1
Fiscal Year
2005
Total Cost
$43,976
Indirect Cost
Name
Stanford University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305