This proposal involves the use of quantum mechanical calculations and subsequent analysis to examine the electronic structure of dinuclear and polynuclear Fe-O complexes and Mn-O complexes as relevant models for active sites of metalloprotein systems. Fe-O complexes are found in: (a) ribonucleotide reductase, (b) methane monooxygenase, (c) purple acid phosphatases,and (d) hemerythrin. A polynuclear Mn-O complex occurs at the active site in the oxygen evolving complex of photosystem II. All of our calculations will be of the Xalpha or local spin density self consistent field type. We will systematically study relevant model complexes as a function of oxidation state, coordination geometry, and binding of substrate ligands or reaction intermediates. The calculations will be compared with experimental results by magnetic susceptibility, and by Mossbauer, electron spin resonance and/or optical spectroscopies for proteins and synthetic analogues. Further, we will examine electron density distributions and spin density distributions in some detail since these features should be closely associated with catalytic mechanism. Qualitative and quantitative ligand binding energetics will also be explored. Our goal is to relate predicted and experimental properties as well as to gain insight into catalytic function and regulation in these enzymes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM043278-02
Application #
3302317
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1991-05-01
Project End
1996-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Luber, Sandra; Leung, Sophie; Herrmann, Carmen et al. (2014) EXAFS simulation refinement based on broken-symmetry DFT geometries for the Mn(IV)-Fe(III) center of class I RNR from Chlamydia trachomatis. Dalton Trans 43:576-83
Fu, Li; Xiao, Dequan; Wang, Zhuguang et al. (2013) Chiral sum frequency generation for in situ probing proton exchange in antiparallel ?-sheets at interfaces. J Am Chem Soc 135:3592-8
Xiao, Dequan; Fu, Li; Liu, Jian et al. (2012) Amphiphilic adsorption of human islet amyloid polypeptide aggregates to lipid/aqueous interfaces. J Mol Biol 421:537-47
Rivalta, Ivan; Brudvig, Gary W; Batista, Victor S (2012) Oxomanganese complexes for natural and artificial photosynthesis. Curr Opin Chem Biol 16:11-8
Han, Wen-Ge; Noodleman, Louis (2011) DFT calculations for intermediate and active states of the diiron center with a tryptophan or tyrosine radical in Escherichia coli ribonucleotide reductase. Inorg Chem 50:2302-20
Han, Wen-Ge; Sandala, Gregory M; Giammona, Debra Ann et al. (2011) Mossbauer properties of the diferric cluster and the differential iron(II)-binding affinity of the iron sites in protein R2 of class Ia Escherichia coli ribonucleotide reductase: a DFT/electrostatics study. Dalton Trans 40:11164-75
Rivalta, Ivan; Amin, Muhamed; Luber, Sandra et al. (2011) Structural-functional role of chloride in photosystem II. Biochemistry 50:6312-5
Luber, Sandra; Rivalta, Ivan; Umena, Yasufumi et al. (2011) S1-state model of the O2-evolving complex of photosystem II. Biochemistry 50:6308-11
Watt, Eric D; Rivalta, Ivan; Whittier, Sean K et al. (2011) Reengineering rate-limiting, millisecond enzyme motions by introduction of an unnatural amino acid. Biophys J 101:411-20
Han, Wen-Ge; Noodleman, Louis (2010) Quantum cluster size and solvent polarity effects on the geometries and Mössbauer properties of the active site model for ribonucleotide reductase intermediate X: a density functional theory study. Theor Chem Acc 125:305-317

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