XAFS data of native TBADH has been collected on zinc and cobalt K-edges. Analysis of EXAFS and edge data of native enzyme and its metal derivatives will provide the ground base for the assignment of coordination environment and accurate metal-ligand distances at the active site. Inhibition Studies: XAFS measurements on inhibited TBADH were conducted using TBADH-DMSO (dimethyl sulfoxide) complex. DMSO is known to inhibit ALDH in a transition state manner. X-ray crystallography studies of ALDH-DMSO complexes show that the DMSO ligand is directly bound to the catalytic zinc ion. XAFS and edge data will be collected on native TBADH and Cd/Co substituted TBADH complexed with DMSO. Assigning the coordination environment and metal-ligand distances of the active site in TBADH-DMSO complex will provide the structure of the transition state analogue of TBADH and a relevant structural intermediate in the catalytic pathway. SCIENTICIC SUBPROJECT 60

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001633-19
Application #
6491487
Study Section
Project Start
2001-09-01
Project End
2002-08-31
Budget Start
Budget End
Support Year
19
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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