MARC 主機 00000nam  2200349   4500 
001    AAI3253524 
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035    (UMI)AAI3253524 
040    UMI|cUMI 
100 1  Pau, Monita Yuen-Ming 
245 10 Spectroscopic and computational studies of the intradiol 
       and extradiol dioxygenases:  Understanding oxygen 
       activation by ferrous and ferric non-heme iron active 
300    196 p 
500    Source: Dissertation Abstracts International, Volume: 68-
       02, Section: B, page: 0966 
500    Adviser:  Edward I. Solomon 
502    Thesis (Ph.D.)--Stanford University, 2007 
520    Mononuclear non-heme iron enzymes catalyze a wide range of
       biological reactions involving O2. A sub-class of these 
       enzymes is the catechol dioxygenases. They are mostly 
       found in soil bacteria but related enzymes are also found 
       in humans. They catalyze the ring cleavage of catecholic 
       substrates by inserting both atoms of O2 into the aromatic
       ring. Based on the position of ring cleavage, the catechol
       dioxygenases are further divided into intradiol and 
       extradiol dioxygenases. These enzymes have different 
       residues around the iron center and differ in metal 
       oxidation states and reaction mechanisms. Intradiol 
       dioxygenases employ a Fe3+ center to activate the 
       substrate for direct attack by O2 and insert O2 between 
       the vicinal hydroxyl groups to yield muconic acids 
       derivatives. Alternatively, extradiol dioxygenases use a 
       Fe2+ center to activate O 2 and incorporate both atoms of 
       O2 adjacent to the vicinal diols to yield muconic 
       semialdehyde products. The significance of these enzymes 
       lies in their role in bioremediation, and mutations in 
       human enzymes are associated with genetic diseases 
520    Oxygen intermediates are often too labile to be trapped 
       for spectroscopic studies; therefore we applied a 
       combination of experiments and theoretical calculations on
       a series of anaerobic species to evaluate the similarities
       and differences in these enzymes. To understand how the 
       Fe3+ site activates the substrate in intradiol 
       dioxygenases, we characterized the geometric and 
       electronic structures of the anaerobic enzyme-substrate 
       complex by using variable-temperature variable-field 
       magnetic circular dichroism spectroscopy and density 
       functional theory (DFT) calculations. We further developed
       a theoretical model to explain how triplet O2 interacts 
       with singlet catechol in this formally spin-forbidden 
       reaction. To understand how the Fe 2+ site activates O2 in
       extradiol dioxygenases, we used NO as an O2 analogue to 
       study potential FeO2 intermediates in the protein-
       catalyzed reactions. We developed an experimentally 
       calibrated DFT protocol for {FeNO}7 complexes using a well
       -characterized model system. By applying this DFT 
       methodology on the enzyme-nitrosyl complexes and 
       complementing the results by spectroscopic data, we have 
       laid the foundation necessary for the investigation of the
       O2 reaction coordinate of extradiol dioxygenases and 
       identification of factors governing the specificity of 
       ring cleavage in the catechol dioxygenases 
590    School code: 0212 
590    DDC 
650  4 Chemistry, Biochemistry 
650  4 Chemistry, Inorganic 
650  4 Chemistry, Physical 
690    0487 
690    0488 
690    0494 
710 2  Stanford University 
773 0  |tDissertation Abstracts International|g68-02B 
856 40 |u