| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
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| Initial Amendment Date: | April 25, 2005 |
| Latest Amendment Date: | March 26, 2009 |
| Award Number: | 0446395 |
| Award Instrument: | Continuing Grant |
| Program Manager: |
Holly Ellis
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | April 15, 2005 |
| End Date: | March 31, 2011 (Estimated) |
| Total Intended Award Amount: | $960,332.00 |
| Total Awarded Amount to Date: | $1,203,936.00 |
| Funds Obligated to Date: |
FY 2007 = $475,526.00 FY 2009 = $255,905.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
1608 4TH ST STE 201 BERKELEY CA US 94710-1749 (510)643-3891 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
1608 4TH ST STE 201 BERKELEY CA US 94710-1749 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | Molecular Biophysics |
| Primary Program Source: |
app-0107 01000910DB NSF RESEARCH & RELATED ACTIVIT |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
The relationship between protein motions and catalytic efficiency is one of the least understood aspects of the enormous catalytic power of enzymes. Our ability to describe and predict this relationship has wide ranging implications for the de novo design of new protein catalysts. This project is focused on a highly related family of enzymes that catalyze alcohol oxidation (alcohol dehydrogenases, ADHs) that function in the range of 5C (psychrophilic ADH), 25C (mesophilic ADH) and 70C (thermophilic ADH). In each case, the ADH catalyzes the transfer of one hydrogen plus two electrons (hydride ion) from substrate to cofactor. Previous work has shown first, that these reactions occur with substantial tunneling of the hydride ion and second, that hydrogen tunneling must be linked to dynamical features within the protein. The comparison of proteins that function in different temperature niches, with different inherent dynamical and stability properties, provides a powerful experimental handle in the efforts to link protein motions and catalysis. The project will combine a range of kinetic and spectroscopic experiments that allow the P.I. to examine the properties of hydrogen transfer and protein dynamical features, respectively. Kinetic probes of hydrogen transfer will include the temperature dependence of rate and kinetic isotope effects as well as the relationship of this behavior among the three isotopes of hydrogen (protium, deuterium and tritium). Spectroscopic probes of protein dynamics will include the use of hydrogen/deuterium exchange, linked to mass spectrometry, protein fluorescence and nuclear magnetic resonance.
Broader Impacts: This work is at the cutting edge of enzymology and will provide information that is directly relevant to the de novo design of new catalysts. The project is training a cadre of young personnel at different stages of careers. The project will involve training of the scientific workforce. There will be opportunities for undergraduate and graduate student research. In addition, mentoring of postdoctoral associates and beginning faculty members is an integral part of this research.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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