This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this project is to seek experimental evidence to support the recent hypothesis that enzymes obtain the energy needed for catalysis by forming very strong, low-barrier, hydrogen bonds in the transition state, or in otherwise unstable intermediates, while having only weak hydrogen bonds in the ground state. Low-barrier hydrogen bonds have very low field proton NMR chemical shifts, and we will look for such low field signals in enzyme complexes where we think, from other evidence, that they should be present. For example, we will look at fumarase complexed with chlorofumarate, 3-nitrolactate, or 3-nitropropionate, since such complexes should mimic the enolized 'carbanion' intermediate in the reaction which we believe must be stabilized by low-barrier hydrogen bonds. Low-barrier hydrogen bonds also have low deuterium fractionation factors, which can be measured by integrating the NMR peaks in mixed H2O and D2O solvent. We will measure the fractionatio n factors of any low field peaks we find in fumarase complexes, and also the fractionation factors of the low field peaks previously seen in the NMR spectra of aspartate transaminase.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR002301-21A1
Application #
7420538
Study Section
Special Emphasis Panel (ZRG1-BCMB-E (40))
Project Start
2006-04-20
Project End
2007-02-28
Budget Start
2006-04-20
Budget End
2007-02-28
Support Year
21
Fiscal Year
2006
Total Cost
$982
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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