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Characterization of the hepatitis C ...

Pang, Phillip Soon-Ho.

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Characterization of the hepatitis C viral helicase, and, a sequence analysis algorithm that predicts functional interactions.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Characterization of the hepatitis C viral helicase, and, a sequence analysis algorithm that predicts functional interactions./
作者:	Pang, Phillip Soon-Ho.
面頁冊數:	190 p.
附註:	Adviser: Anna Marie Pyle.
Contained By:	Dissertation Abstracts International63-10B.
標題:	Biology, Microbiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3066886
ISBN:	0493862986

Characterization of the hepatitis C viral helicase, and, a sequence analysis algorithm that predicts functional interactions.
Pang, Phillip Soon-Ho.

Characterization of the hepatitis C viral helicase, and, a sequence analysis algorithm that predicts functional interactions. - 190 p.

Adviser: Anna Marie Pyle.

Thesis (Ph.D.)--Columbia University, 2002.

The Hepatitis C Virus (HCV) is a cytoplasmically replicating RNA virus that is a major worldwide health problem. The Hepatitis C viral protein NS3 is a protease/helicase that plays an essential role in the life cycle of this virus. NS3 is therefore an important drug target in the effort to combat HCV. Most work, however, has focused on the protease, rather than the helicase activities of the enzyme. In order to better characterize NS3 helicase activity, we evaluated individual stages of duplex unwinding by NS3 alone and in complex with cofactor NS4A. Despite a putative replicative role in RNA unwinding, we found that NS3 alone is a surprisingly poor helicase on RNA, but that RNA activity is promoted by cofactor NS4A. In contrast, NS3 alone is a highly processive helicase on DNA. Phylogenctic analysis suggests that this robust DNA helicase activity is not vestigial, and may have specifically evolved in HCV. Given that HCV has no replicative DNA intermediate, these findings suggest that NS3 may have the capacity to affect host DNA.

ISBN: 0493862986Subjects--Topical Terms:

1017734
Biology, Microbiology.

Characterization of the hepatitis C viral helicase, and, a sequence analysis algorithm that predicts functional interactions.
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502 $a Thesis (Ph.D.)--Columbia University, 2002.
520 $a The Hepatitis C Virus (HCV) is a cytoplasmically replicating RNA virus that is a major worldwide health problem. The Hepatitis C viral protein NS3 is a protease/helicase that plays an essential role in the life cycle of this virus. NS3 is therefore an important drug target in the effort to combat HCV. Most work, however, has focused on the protease, rather than the helicase activities of the enzyme. In order to better characterize NS3 helicase activity, we evaluated individual stages of duplex unwinding by NS3 alone and in complex with cofactor NS4A. Despite a putative replicative role in RNA unwinding, we found that NS3 alone is a surprisingly poor helicase on RNA, but that RNA activity is promoted by cofactor NS4A. In contrast, NS3 alone is a highly processive helicase on DNA. Phylogenctic analysis suggests that this robust DNA helicase activity is not vestigial, and may have specifically evolved in HCV. Given that HCV has no replicative DNA intermediate, these findings suggest that NS3 may have the capacity to affect host DNA.
520 $a Additionally, a novel, automated sequence analysis algorithm has been designed that is capable of predicting function interactions between residues. This algorithm is uniquely applicable to any type of biopolymer, including RNAs and proteins, as well as combinations of different biopolymers. This algorithm, entitled SHEVEK, yields accurate results despite using alignments of only a small number of sequences. The versatility and accuracy of the algorithm is demonstrated by the prediction of interactions within RNAs and modified RNAs, within proteins, as well as through the prediction of RNA-protein and protein-protein interactions.
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