東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Structure, function, and inhibition ...

University of Illinois at Chicago.

Linked to FindBook

Google Book

Amazon

博客來

Structure, function, and inhibition of the papain-like protease from SARS coronavirus.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Structure, function, and inhibition of the papain-like protease from SARS coronavirus./
Author:	Ratia, Kiira.
Description:	231 p.
Notes:	Adviser: Andrew D. Mesecar.
Contained By:	Dissertation Abstracts International70-01B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3345539
ISBN:	9781109001396

Structure, function, and inhibition of the papain-like protease from SARS coronavirus.
Ratia, Kiira.

Structure, function, and inhibition of the papain-like protease from SARS coronavirus. - 231 p.

Adviser: Andrew D. Mesecar.

Thesis (Ph.D.)--University of Illinois at Chicago, 2008.

The coronavirus responsible for severe acute respiratory syndrome (SARS-CoV) relies on two proteases during viral replication. The biochemical, kinetic, and structural properties of the SARS-CoV papain-like protease (PLpro) were analyzed in order to effectively discover novel protease inhibitors targeting this enzyme.

ISBN: 9781109001396Subjects--Topical Terms:

1017734
Biology, Microbiology.

Structure, function, and inhibition of the papain-like protease from SARS coronavirus.
LDR:03125nam 2200313 a 45 001 855258
005 20100708
008 100708s2008 ||||||||||||||||| ||eng d
020 $a 9781109001396
035 $a (UMI)AAI3345539
035 $a AAI3345539
040 $a UMI $c UMI
100 1 $a Ratia, Kiira. $3 1021823
245 1 0 $a Structure, function, and inhibition of the papain-like protease from SARS coronavirus.
300 $a 231 p.
500 $a Adviser: Andrew D. Mesecar.
500 $a Source: Dissertation Abstracts International, Volume: 70-01, Section: B, page: 0149.
502 $a Thesis (Ph.D.)--University of Illinois at Chicago, 2008.
520 $a The coronavirus responsible for severe acute respiratory syndrome (SARS-CoV) relies on two proteases during viral replication. The biochemical, kinetic, and structural properties of the SARS-CoV papain-like protease (PLpro) were analyzed in order to effectively discover novel protease inhibitors targeting this enzyme.
520 $a The catalytic core domain of PLpro was cloned, expressed, and purified to homogeneity. In order to kinetically characterize PLpro, a fluorescence-based assay was developed. Different fluorescent probes and substrates, including ubiquitin-related molecules, were explored to optimize the assay for high-throughput screening trials and kinetic analyses. The kinetics of both SARS-CoV PLpro and the related coronaviral protease HCoV-NL63 PLP2 were analyzed to gain insight into the reaction mechanism catalyzed by this group of enzymes.
520 $a The SARS-CoV PLpro domain was crystallized, and the resulting X-ray crystal structure was solved using isomorphous replacement. Important structural features of PLpro include an intact catalytic triad, a zinc-binding domain, an N-terminal ubiquitin-like domain, and an overall resemblance to structures of human deubiquitinating enzymes.
520 $a To identify potential inhibitors of PLpro, a fluorescence-based high-throughput screen was developed to screen 50,000 compounds. Two hits were explored as initial leads through structure-activity relationships of synthetic analogs. The IC50 values of each group of compounds were improved >40-fold. The most potent inhibitors were found to have antiviral activity against SARS-CoV-infected cells without producing significant cellular toxicity. Kinetic and biochemical studies established that the inhibitors bind reversibly and are competitive against substrates, yet they cause irreversible inactivation of the enzyme. The inhibitors were found to be selective for PLpro over human deubiquitinating enzymes. The crystal structure of PLpro with one of the lead inhibitors was solved and reveals that the inhibitor binds in the S3 and S4 sites of the enzyme, causing loop movement around the active site and potentially triggering irreversible oxidation of the catalytic cysteine.
590 $a School code: 0799.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Biology, Virology. $3 1019068
690 $a 0410
690 $a 0720
710 2 $a University of Illinois at Chicago. $3 1020478
773 0 $t Dissertation Abstracts International $g 70-01B.
790 $a 0799
790 1 0 $a Mesecar, Andrew D., $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3345539