The goal of this work is to improve our understanding of the biological function of vanadium, in general, and to investigate the reactivity of vanadium-containing proteins, more specifically. Vanadium is capable of existing in many oxidation states and the aqueous chemistry of vanadium is dominated by electron transfer, hydrolysis and/or polymerization reactions. Clearly the coordination environment of the vanadium will affect its reactivity. Towards our overall goal, we proposed to investigate the factors that govern the oxidation and reduction reactions of vanadium bound to macromolecules (eg., the naturally occurring V-bromoperoxidase and V substituted derivatives of transferrin, lactoferrin, ovotransferrin, carboxypeptidase A, carbonic anhydrase B, thermolysin, bleomycin, etc), and to examine the possibility that vanadium proteins catalyze the disproportionation of superoxide (i.e., superoxide dismutase activity), participate in the disproportionation of hydrogen peroxide (i.e., catalase activity) and/or halogenate certain organic substrates in the presence of H2O2 (i.e., haloperoxidase activity). We have found that several V(V) complexes catalyze the decomposition of hydrogen peroxide, including V2-transferrin, V(V)-(8- hydroxyuinoline)(O)(OCH3) and V(V)-desferoxamine. The later two are catalyzed by ultraviolet light. We also propose to further characterize the vanadium bromoperoxidase (V-BrPO) isolated from Ascophyllum nodosum and Laminaria setchellii. We have discovered that this enzyme brominates the pyrimidine-containing nucleic acid bases, cytosine and uracil. Experiments are proposed to probe the substrate specificity by variation of the pyrimidine-ring substituents. Experiments are also proposed to probe the function of the vanadium. Does the vanadium act as a Lewis acid catalyst or an electron transfer catalyst, cycling between oxidation states? These mechanistic studies will be further probed using the model complex, V(V)-desferoxamine, which we have shown catalyzes the same bromination reactions as the V-BrPO.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29GM038130-03
Application #
3466144
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Santa Barbara
Department
Type
Schools of Arts and Sciences
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106
Gauglitz, Julia M; Iinishi, Akira; Ito, Yusai et al. (2014) Microbial tailoring of acyl peptidic siderophores. Biochemistry 53:2624-31
Gauglitz, Julia M; Butler, Alison (2013) Amino acid variability in the peptide composition of a suite of amphiphilic peptide siderophores from an open ocean Vibrio species. J Biol Inorg Chem 18:489-97
Gauglitz, Julia M; Zhou, Hongjun; Butler, Alison (2012) A suite of citrate-derived siderophores from a marine Vibrio species isolated following the Deepwater Horizon oil spill. J Inorg Biochem 107:90-5
Vraspir, Julia M; Holt, Pamela D; Butler, Alison (2011) Identification of new members within suites of amphiphilic marine siderophores. Biometals 24:85-92
Sandy, Moriah; Butler, Alison (2011) Chrysobactin siderophores produced by Dickeya chrysanthemi EC16. J Nat Prod 74:1207-12
Owen, Tate; Butler, Alison (2011) Metallosurfactants of bioinorganic interest: Coordination-induced self assembly. Coord Chem Rev 225:678-687
Sandy, Moriah; Han, Andrew; Blunt, John et al. (2010) Vanchrobactin and anguibactin siderophores produced by Vibrio sp. DS40M4. J Nat Prod 73:1038-43
Butler, Alison; Theisen, Roslyn M (2010) Iron(III)-siderophore coordination chemistry: Reactivity of marine siderophores. Coord Chem Rev 254:288-296
Homann, Vanessa V; Edwards, Katrina J; Webb, Eric A et al. (2009) Siderophores of Marinobacter aquaeolei: petrobactin and its sulfonated derivatives. Biometals 22:565-71
Homann, Vanessa V; Sandy, Moriah; Tincu, J Andy et al. (2009) Loihichelins A-F, a suite of amphiphilic siderophores produced by the marine bacterium Halomonas LOB-5. J Nat Prod 72:884-8

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