کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3425836 | 1594268 | 2009 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identifying amino acid residues that contribute to the cellular-DNA binding site on retroviral integrase
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
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![عکس صفحه اول مقاله: Identifying amino acid residues that contribute to the cellular-DNA binding site on retroviral integrase Identifying amino acid residues that contribute to the cellular-DNA binding site on retroviral integrase](/preview/png/3425836.png)
چکیده انگلیسی
Although retroviral integrase specifically trims the ends of viral DNA and inserts these ends into any sequence in cellular DNA, little information is available to explain how integrase distinguishes between its two DNA substrates. We recently described novel integrase mutants that were improved for specific nicking of viral DNA but impaired at joining these ends into nonviral DNA. An acidic or bulky substitution at one particular residue was critical for this activity profile, and the prototypic protein - Rous sarcoma virus integrase with an S124D substitution - was defective at nonspecifically binding DNA. We have now characterized 19 (including 16 new) mutants that contain one or more aspartic acid substitutions at residues that extend over the surface of the protein and might participate with residue 124 in binding cellular DNA. In particular, every mutant with an aspartate substitution at residue 98 or 128, similar to the original S124D protein, showed improved specific nicking of viral DNA but disturbed nonspecific nicking of nonviral DNA. These data describe a probable cellular-DNA binding platform that involves at least 5 amino acids, in the following order of importance: 124Â >Â 128Â >Â (98, 125)Â >Â 123. These experimental data are vital for new models of integrase and will contribute to identifying targets for the next generation of integrase inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 389, Issues 1â2, 20 Juneâ5 July 2009, Pages 141-148
Journal: Virology - Volume 389, Issues 1â2, 20 Juneâ5 July 2009, Pages 141-148
نویسندگان
Matthew G. Nowak, Malgorzata Sudol, Noelle E. Lee, Wesley M. Jr., Michael Katzman,