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Mapping potential new sites for anti...

Yassin, Aymen.

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Mapping potential new sites for antibiotic action in the ribosome.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Mapping potential new sites for antibiotic action in the ribosome./
Author:	Yassin, Aymen.
Description:	196 p.
Notes:	Adviser: Alexander Mankin.
Contained By:	Dissertation Abstracts International67-05B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3218799
ISBN:	9780542701849

Mapping potential new sites for antibiotic action in the ribosome.
Yassin, Aymen.

Mapping potential new sites for antibiotic action in the ribosome. - 196 p.

Adviser: Alexander Mankin.

Thesis (Ph.D.)--University of Illinois at Chicago, Health Sciences Center, 2006.

The ribosome is the main target for antibiotics that inhibit protein synthesis. These drugs bind primarily to rRNA. Despite their chemical diversity, the binding of these compounds is limited to few overlapping sites corresponding to some of the known functional centers. For a multimolecular complex like the ribosome with its enormous size and multifaceted activity, other unexplored functional regions must exist. These new functional sites can serve as potential targets for new antibiotics in this clinically validated target.

ISBN: 9780542701849Subjects--Topical Terms:

1017734
Biology, Microbiology.

Mapping potential new sites for antibiotic action in the ribosome.
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020 $a 9780542701849
035 $a (UMI)AAI3218799
035 $a AAI3218799
040 $a UMI $c UMI
100 1 $a Yassin, Aymen. $3 1291584
245 1 0 $a Mapping potential new sites for antibiotic action in the ribosome.
300 $a 196 p.
500 $a Adviser: Alexander Mankin.
500 $a Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2384.
502 $a Thesis (Ph.D.)--University of Illinois at Chicago, Health Sciences Center, 2006.
520 $a The ribosome is the main target for antibiotics that inhibit protein synthesis. These drugs bind primarily to rRNA. Despite their chemical diversity, the binding of these compounds is limited to few overlapping sites corresponding to some of the known functional centers. For a multimolecular complex like the ribosome with its enormous size and multifaceted activity, other unexplored functional regions must exist. These new functional sites can serve as potential targets for new antibiotics in this clinically validated target.
520 $a We have developed a genetic approach to find structurally and functionally critical sites in the ribosome by mapping rRNA positions where nucleotide alterations impair the ribosome activity and lead to a deleterious phenotype. Random mutant libraries were generated by in vivo mutagenesis in a plasmid carrying a ribosomal RNA operon. Fragment exchange was then used to generate random mutant segment-libraries covering the entire length of the ribosomal operon. The segment-libraries were enriched in clones with deleterious rRNA mutations by negative selection. High throughput screening and sequencing were used to identify deleterious mutations in the rRNA.
520 $a A total of 53 single point mutations were identified in the 16S rRNA, and 77 single point mutations were identified in the 23S rRNA. Many of these mutations were mapped to known functional sites, or binding sites to already known antibiotics, therefore validating our approach. More importantly, a number of mutations were located in previously unexplored regions. The collection of deleterious mutations was sorted, and the mutations were ranked according to the severity of their deleterious phenotypes. Several ribosomal regions where the rRNA mutations tend to cluster were identified as potential new antibiotic targets. Several individual mutations within the detected clusters were studied in detail to correlate their effect with the defect they cause in translation. The generated collection of deleterious rRNA mutations can be used in the search for new antibiotic targets and may advance our understanding of the functions of rRNA in translation.
590 $a School code: 0806.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0307
690 $a 0410
690 $a 0487
710 2 0 $a University of Illinois at Chicago, Health Sciences Center. $3 1021703
773 0 $t Dissertation Abstracts International $g 67-05B.
790 $a 0806
790 1 0 $a Mankin, Alexander, $e advisor
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3218799