Statistical, DFT and continuum electrostatics analysis of histidine ligated hemes in the non-redundant heme database in model complexes and in cytochrome c oxidase
Item
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Title
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Statistical, DFT and continuum electrostatics analysis of histidine ligated hemes in the non-redundant heme database in model complexes and in cytochrome c oxidase
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Identifier
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d_2009_2013:8c7fd7265bff:10524
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identifier
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10713
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Creator
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Zhang, Jun,
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Contributor
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Marilyn Gunner
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Date
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2010
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Language
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English
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Publisher
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City University of New York.
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Subject
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Molecular physics | Cytochrome c Oxidase | DFT | Heme | MCCE | statistical survey
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Abstract
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Heme plays an important role in biological oxidation---reduction chemistry. Important heme structural factors of are investigated here to understand how the redox potential is shifted when bound to proteins. A statistical analysis of a non-redundant heme database shows that the redox potentials of heme are significantly correlated with heme types and heme ligand types. The patterns of histidine ligand orientation, relative histidine orientations were investigated for the proteins in the database.;The heme redox potential can be shifted by the existence of hydrogen bond partner to the axial histidine ligand of the heme. With the simplified model complex of Bis-Imidazole-Porphyrin, the redox potential shift due to the hydrogen bond was compared using DFT and Continuum electrostatics methods. Two models, with a representative hydrogen bond partner and point charges, are built for the simulation. The calculated final energy shift due to the hydrogen bond found by the two methods are within 15% of each other. Four different charge sets were compared in the electrostatics calculation. Simulation of Bis-Imidazole-Porphyrin complex using DFT method also revealed the energetic impact of relative orientation of imidazole ligands on either side of the porphryn is less than 1kcal/mol in a flat core porphyrin complex.;Cytochrome c Oxidase is one of the essential proteins in the anaerobic electron transfer chain. In the protein from Rhodobactor sphaeroides, S44 makes a hydrogen bond to H102, the axial ligand of Heme a, a key cofactor on the reaction pathway electron transfer chain. The electrochemical behavior of Heme a is revisited with a comparison of wild type and S44D mutant using the continuum electrostatics program MCCE. At pH7, the partially ionized Asp44 lowers the Heme redox potential by 50mV. The DeltaG° between Cu A and Heme a is more pH-dependant with Asp than Ser. Holding other cofactors oxidized, electron transfer from CuA to Heme a is coupled with uptake 0.6 and 1.1 protons in S44 and D44 structures respectively.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Physics
