This research will encompass two distinct projects in the area of biomolecular structure-function studies: 1) Construction of selected mutants of E. coli dihydrofolate reductase (DHFR); by x-ray crystallography observe the structural perturbations effected by these mutations; and characterize the catalytic properties of the mutant enzymes by steady-state and pre-steady-state kinetic methods, focusing on individual elementary steps in the pathway. The goal of this project is to answer various fundamental questions about the stereochemical mechanism that arise upon examination of crystal structures of E. coli DHFR and three other species of DHFR previously determined in this laboratory. 2) X-ray crystallographic structure determination of several lymphokines, including especially interleukin-2 and interferon- alpha. The lymphokines are a class of protein molecules that act as intercellular signals of the immune system. It is hoped to identify and examine the chemical geometry of the sites on these molecules that interact with their receptors and thereby elicit biological activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM010928-26
Application #
3268182
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1977-01-01
Project End
1993-01-31
Budget Start
1988-02-01
Budget End
1989-01-31
Support Year
26
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Pelletier, H; Sawaya, M R; Kumar, A et al. (1994) Structures of ternary complexes of rat DNA polymerase beta, a DNA template-primer, and ddCTP. Science 264:1891-903
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Howell, E E; Villafranca, J E; Warren, M S et al. (1986) Functional role of aspartic acid-27 in dihydrofolate reductase revealed by mutagenesis. Science 231:1123-8

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