This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Corrinoid-dependent enzymes are widespread in nature and play key roles in human, animal and microbial metabolism. Two known B12-dependent enzymes exist in humans: methylcobalamin (MeCbl)-dependent methionine synthase and adenosylcobalamin (AdoCbl)-dependent methylmalonyl-coenzyme A mutase. The clinical hallmarks of B12 deficiency are megaloblastic anemia ( pernicious anemia ), and/or neuropathies. Upon reaching cells, cobalamin derivatives are converted to MeCbl and AdoCbl by currently ill-defined mechanisms. Many studies have been carried out over the past several decades involving the extraction and identification of cobalamins from mammalian cells, tissue and blood, in addition to other biological samples such as foods and seaweed. Adenosylcobalamin, methylcobalamin and aquacobalamin are the major cobalamin metabolites isolated from biological samples but there are also reports of the isolation of nitrocobalamin and sulfitocobalamin from biological sources, along with other unknown complexes. We have synthesized a number of cobalamin derivatives to assist in the identification of unknown cobalamins isolated from biological samples, and we have determined the crystal structures of a number of these complexes including N-acetylcysteinylcobalamin, nitrosocobalamin and aquocobalamin at atomic resolution (< 0.8 ) using high energy X-rays (> 15000 eV) and very short crystal-detector distances. The data collected at SSRL is comparable to, and in some cases better than the data collected using conventional methods (which generally employ Mo-Kalpha radiation).

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-28
Application #
7598097
Study Section
Special Emphasis Panel (ZRG1-BPC-E (40))
Project Start
2007-03-01
Project End
2008-02-29
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
28
Fiscal Year
2007
Total Cost
$993
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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