Metal Ion Probes Membrane Protein Structure and Function
Michael Bowman, Principal Investigator
Funding Agency: National Institutes of Health, National Institute of General Medical Sciences
The focus of the Metal Ion Probes Membrane Protein Structure and Function project at Pacific Northwest National Laboratory (PNNL) is to understand the basis for the specific structure-function relationship in complex protein reactions by examining differences and similarities between analogous proteins from different organisms. This approach will help us understand the natural variation in protein structure, function, and other properties between different isoforms or different species and is a necessary complement to the study of site-directed mutants of a single protein. This effort is part of a long-term interest in the use of electron paramagnetic resonance (EPR) as a structural probe and draws on experience in developing and applying innovative EPR methods for answering specific biological and physical questions. Our work will provide insights into the bioenergetically important cytochrome bc-type complex and the metabolically important eukaryotic cytochrome P450 enzymes. Such insights could lead to new, highly selective drugs and antibiotics that exploit differences between these proteins in different organisms or between different isoforms in humans. The methods developed in carrying out this work will be broadly applicable to other membrane proteins and other protein complexes.
