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. Nitrile hydratase (NHase) is an enzyme activity found in a number of soil bacteria which catalyzes conversion of organic nitriles to organic amides. Various nitrile hydratase enzymes have either an iron or cobalt atom present at the active site. These enzymes are unusual in that the active site metal resides in an N2S3 coordination environment comprised of amide nitrogen atoms and oxidized sulfur atoms. This project involves the synthesis of 'model complexes' which will closely mimic the immediate structure of the iron or cobalt centers of the enzyme. By studying the structures, spectroscopy, and reactivity of these complexes it will be possible to determine what features are required for the iron or cobalt atom to effectively carry out the chemistry and potentially to develop synthetic systems which will be able to reproduce or even improve upon this reactivity. These studies are important not only for the information they will provide regarding the catalytic mechanism of NHase, but also for information that can be applied to other metalloenzymes with similar active-site features. We have structurally characterized the first cobalt complex which has two nitrogen and three sulfur atoms bound to the cobalt, reproducing the types of atoms that are bound to the cobalt in the native enzyme. This complex contains imine nitrogens, rather than the amide nitrogens in the enzyme. We have also prepared a related model complex which incorporates amide nitrogens and oxidized sulfurs. Further studies on the catalytic activity of these and related models will address the importance of these features.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017708-05
Application #
7381955
Study Section
Special Emphasis Panel (ZRR1-RI-A (03))
Project Start
2006-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$48,952
Indirect Cost
Name
University of Kansas Lawrence
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
076248616
City
Lawrence
State
KS
Country
United States
Zip Code
66045
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