Computational studies of structure-function relationships in the bacteriophage lambda repressor.
Item
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Title
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Computational studies of structure-function relationships in the bacteriophage lambda repressor.
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Identifier
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AAI9707117
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identifier
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9707117
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Creator
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Kombo, David Caleb.
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Contributor
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Advisers: George Nemethy | S. Rackovsky | Harold A. Scheraga
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Date
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1996
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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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Biophysics, General | Biology, Molecular
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Abstract
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We have carried out conformational energy computations to find the most favorable packing at the dimer interface of mutants of the {dollar}\lambda{dollar} repressor. We find that whether or not a mutant binds DNA depends primarily on whether the structure of the dimerization interface allows the recognition helix of each monomer to fit into its recognition site on the DNA. The presence of DNA-binding activity correlates well with the predicted interhelical geometrical parameters and the number of contacts involving the residues at position 84 and 87. The hydrogen bonds between the peptide carbonyl oxygen of Tyr-85 and the peptide NH group of the residue at position 89 in active mutants are longer and less linear than their corresponding ones in inactive mutants. We have also carried out theoretical studies of the changes caused by substituting 5-hydroxytryptophan for tryptophan in: (a) The single amino acid with acetyl and methyl capping group, (b) a poly-alanine alpha helix containing a single tryptophan, and dimerization interface of the N-terminal domain of the {dollar}\lambda{dollar} repressor. We find that the hydroxyl group induces only minor perturbations in all these systems. These results suggest that replacement of Trp by its analog 5-hydroxyTrp in studies of protein-DNA binding will generally be tolerated.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
