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 focus of our research is to understand how gaseous messengers such as NO, CO, and O2 transduce signals via hemoprotein sensors. We have begun to address this by solving crystal structures of key heme-containing proteins that either biosynthesize the messenger or get activated by it. The first project is related to our discovery of a novel ancestral nitric oxide synthases (NOS) in bacteria, which like the eukaryotic enzymes are dimeric, but lack the Zn-binding domain. In addition, they do not utilize tetrahydrobiopterin as a cofactor. The second project concerns the structure of soluble guanylyl cyclase (sGC), which binds NO and catalyzes the conversion of GTP to cGMP. Identification of the electron-transfer pathway in NOS and determination of the structural determinants of NOS-inhibitor interactions form the basis of the third project. The structural features of NOS-cofactor interactions are also of interest. We have focused our efforts on elucidating the chemical reactivity and shape-based molecular recognition at work in NOS binding sites. The fourth project deals with identifying the molecular basis of how oxygen binding to one domain mediates aerotaxis via structural changes at another domain. Structures of bNOS, sGC, and the aerotransducer are unknown.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-27
Application #
7370336
Study Section
Special Emphasis Panel (ZRG1-BPC-E (40))
Project Start
2006-03-01
Project End
2007-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
27
Fiscal Year
2006
Total Cost
$5,787
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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