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Specific recognition of DNA by natural transcription factors and miniature protein mimics.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Specific recognition of DNA by natural transcription factors and miniature protein mimics.
Author:	Montclare, Jin Kim.
Description:	311 p.
Notes:	Director: Alanna Schepartz.
Notes:	Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2194.
Contained By:	Dissertation Abstracts International64-05B.
Subject:	Chemistry, Organic.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3091762
ISBN:	0496394711

Specific recognition of DNA by natural transcription factors and miniature protein mimics.
Montclare, Jin Kim.

Specific recognition of DNA by natural transcription factors and miniature protein mimics. [electronic resource] - 311 p.

Director: Alanna Schepartz.

Thesis (Ph.D.)--Yale University, 2003.

Chapter three focuses on the design of a miniature protein which mimics the properties of the Q50K engrailed homeodomain. In all previous cases for the design of functional miniature proteins, specific recognition was achieved if the functional epitope was complete---only if every energetically significant contact was included. Disregarding the DNA contact residues from the N-terminal arm of the native protein and grafting only those residue from the DNA recognition helix onto the aPP scaffold, the resultant miniature protein, PPeng4, was able to broadly reproduce the selectivity of the parent protein.

ISBN: 0496394711Subjects--Topical Terms:

193634
Chemistry, Organic.

Specific recognition of DNA by natural transcription factors and miniature protein mimics.
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500 $a Director: Alanna Schepartz.
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502 $a Thesis (Ph.D.)--Yale University, 2003.
520 # $a Chapter three focuses on the design of a miniature protein which mimics the properties of the Q50K engrailed homeodomain. In all previous cases for the design of functional miniature proteins, specific recognition was achieved if the functional epitope was complete---only if every energetically significant contact was included. Disregarding the DNA contact residues from the N-terminal arm of the native protein and grafting only those residue from the DNA recognition helix onto the aPP scaffold, the resultant miniature protein, PPeng4, was able to broadly reproduce the selectivity of the parent protein.
520 # $a Chapter two details the investigation of miniature DNA-binding proteins based on two different bZIP proteins: GCN4 and C/EBP. Previously, these miniature proteins were designed using the protein grafting approach where all the residues required for DNA-recognition of the natural protein are figuratively grafted onto the stable scaffold of aPP (avian pancreatic polypeptide). Examining the affinity and specificity of previous and two new miniature proteins: one that is constrained by a disulfide bond and another which appends the evolved polyproline helix onto a different alpha-helical epitope, our results reveal that the aPP scaffold contributes to the affinity and selectivity for target DNA.
520 # $a This dissertation focuses on the characterization of DNA binding affinity and specificity of natural transcription factors and miniaturized transcription factor mimics. Chapter one describes studies of the DNA binding specificity of the bZIP protein CREB (cyclic-AMP response element binding protein), which discriminates effectively in vivo and in vitro between the 10 base pair cAMP response element (CRE: ATGACGTCAT) and the 9 base pair activating protein 1 (AP-1: ATGACTCAT) site. Using alanine scanning mutagenesis, our results show that specificity is increased by the presence of four glutamic acid residues scattered across the bZIP element and decreased by the presence of two basic residues that flank the conserved DNA contact residue asparagine 22. All of the residues that influence specificity in a significant way are located on the solvent-exposed face of the protein-DNA complex and likely participate in electrostatic interactions between proteins, not between protein and DNA.
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