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Biophysical and computational investigations of protein-protein interactions in mitochondria-dependent apoptosis

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Biophysical and computational investigations of protein-protein interactions in mitochondria-dependent apoptosis
作者:	Cresson, Catherine Michelle.
面頁冊數:	250 p.
附註:	Advisers: George L. McLendon; Salvatore Torquato.
附註:	Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0202.
Contained By:	Dissertation Abstracts International65-01B.
標題:	Chemistry, Biochemistry.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3120411
ISBN:	0496677829

Biophysical and computational investigations of protein-protein interactions in mitochondria-dependent apoptosis
Cresson, Catherine Michelle.

Biophysical and computational investigations of protein-protein interactions in mitochondria-dependent apoptosis [electronic resource] - 250 p.

Advisers: George L. McLendon; Salvatore Torquato.

Thesis (Ph.D.)--Princeton University, 2004.

A binding interaction between two pro-apoptotic proteins, Smac and cytochrome c was measured by 1H NMR, which showed a stoichiometry of 2:1 and a strong ionic strength dependence. Under physiological conditions, the association constant is around 1 x 103 M-1 . Therefore, the binding of Smac and cytochrome c must be accounted for in detailed models of protein release from the mitochondria during apoptosis.

ISBN: 0496677829Subjects--Topical Terms:

226900
Chemistry, Biochemistry.

Biophysical and computational investigations of protein-protein interactions in mitochondria-dependent apoptosis
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500 $a Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0202.
502 $a Thesis (Ph.D.)--Princeton University, 2004.
520 # $a A binding interaction between two pro-apoptotic proteins, Smac and cytochrome c was measured by 1H NMR, which showed a stoichiometry of 2:1 and a strong ionic strength dependence. Under physiological conditions, the association constant is around 1 x 103 M-1 . Therefore, the binding of Smac and cytochrome c must be accounted for in detailed models of protein release from the mitochondria during apoptosis.
520 # $a A novel reduced dimension computational approach to small molecule-protein binding was also developed and successfully tested on the Smac:BIR3 binding system. This two-dimensional approach reproduces the experimental binding trend measured by the fluorescence assay and also performs as well or better than another widely available protein binding program, DOCK. This computational approach was then further expanded to three dimensions employing structural and experimental work previously established about the Smac and BIR3 binding interaction. However, to be successful, the previously applied minimalist approach breaks down as the addition of too many explicit conditions is necessary to produce adequate results.
520 # $a One of these proteins, Smac, also activates apoptosis by binding to the BIR3 domain of XIAP. Smac recognizes a surface groove on BIR3 with only an N-terminal tetramer, AWL The binding constant for BIR3 and a Smac-based dye construct, AVPC-badan, was measured by fluorescence as 0.31 muM. The fluorescence assay was also utilized to determine the binding effects of d-amino acids and double amino acid substitutions of AVPI. At the first two positions, the d-amino acids abolish the binding to BIR3, but at the forth position a d-phenylalanine residue has little effect on the binding strength. Doubly substituted peptides, like ALPF, and AAPF, bind to BIR3 with a strength in between their single substitution counterparts.
520 # $a Protein-protein interactions are difficult to study both experimentally and computationally, but they are critical to many cell signaling pathways. This research focuses on protein complexes in the apoptotic signaling network. Apoptosis is an essential process in the development, homeostasis, and disease of multicellular organisms. It is regulated by an extensive biochemical network of checkpoints and feedback loops, which depends on numerous protein interactions. Understanding the fundamentals of these protein interactions is integral to elucidating the mechanism of apoptosis.
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790 1 0 $a McLendon, George L., $e advisor
790 1 0 $a Torquato, Salvatore, $e advisor
791 $a Ph.D.
792 $a 2004
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