The overall goal of this research program is to study the structure and function of metal sites in biological systems. Primary emphasis is on the insight that can be gained via electron paramagnetic resonance (EPR) spectroscopy. A special interest is biological molecules that contain interacting unpaired spins. The methods include studies of biological molecules with two interacting electron spins or interacting electron and nuclear spins that are intrinsic to the system or added as probes, computer simulations of interacting spins, and calibrations with small molecules selected to test models of the interaction. The proposed work will examine four biological systems to obtain the following information. (1) EPR and electron spin echo envelope modulation will be used to apply our new model of the coordination of metals in transferrin and lactoferrin to the changes in the environments caused by interactions with nonsynergistic ions, with the goal of understanding metal release. (2) Analysis of spin-spin interactions involving Fe and spin labels in hemoglobin will be used to calibrate distance measurement techniques in a system for which X-ray crystallographic structural details are available for the spin-labeled hemoglobin. (3) The distance between nickel and iron-sulfur clusters in hydrogenases will be determined by analysis of EPR spectra due to spin-coupling applying our sophisticated computer simulation capabilities. (4) The lower limit for interspin distances for cases in which resolved spin-spin splitting of EPR signals is not observed will be calculated, providing a synthesis of the insights obtained in this project. (5) The distance between the reactive sulfhydryl group and the Cr(III)ATP binding site in SR CaATPase will be measured, applying our new model of relaxation time changes to studies of Cr-nitroxyl interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021156-17
Application #
3270292
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1977-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
17
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Denver
Department
Type
Schools of Arts and Sciences
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80208
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