skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase

Abstract

Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.

Authors:
 [1];  [2];  [1]; ;  [3];  [1];  [2]
  1. Department of Medicine, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Mail Services H036, Hershey, PA 17033 (United States)
  2. (United States)
  3. Department of Pharmacology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033 (United States)
Publication Date:
OSTI Identifier:
22150076
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 433; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; BINDING ENERGY; DMSO; DNA; ELECTRONS; GLYCOLS; MOLECULAR WEIGHT; SUBSTRATES

Citation Formats

Ealy, Julie B., Department of Chemistry, Penn State Lehigh Valley, 2809 E. Saucon Valley Road, Center Valley, PA 18034, Sudol, Malgorzata, Krzeminski, Jacek, Amin, Shantu, Katzman, Michael, E-mail: mkatzman@psu.edu, and Department of Microbiology and Immunology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase. United States: N. p., 2012. Web. doi:10.1016/J.VIROL.2012.07.022.
Ealy, Julie B., Department of Chemistry, Penn State Lehigh Valley, 2809 E. Saucon Valley Road, Center Valley, PA 18034, Sudol, Malgorzata, Krzeminski, Jacek, Amin, Shantu, Katzman, Michael, E-mail: mkatzman@psu.edu, & Department of Microbiology and Immunology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase. United States. doi:10.1016/J.VIROL.2012.07.022.
Ealy, Julie B., Department of Chemistry, Penn State Lehigh Valley, 2809 E. Saucon Valley Road, Center Valley, PA 18034, Sudol, Malgorzata, Krzeminski, Jacek, Amin, Shantu, Katzman, Michael, E-mail: mkatzman@psu.edu, and Department of Microbiology and Immunology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033. Sat . "Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase". United States. doi:10.1016/J.VIROL.2012.07.022.
@article{osti_22150076,
title = {Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase},
author = {Ealy, Julie B. and Department of Chemistry, Penn State Lehigh Valley, 2809 E. Saucon Valley Road, Center Valley, PA 18034 and Sudol, Malgorzata and Krzeminski, Jacek and Amin, Shantu and Katzman, Michael, E-mail: mkatzman@psu.edu and Department of Microbiology and Immunology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033},
abstractNote = {Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.},
doi = {10.1016/J.VIROL.2012.07.022},
journal = {Virology},
issn = {0042-6822},
number = 1,
volume = 433,
place = {United States},
year = {2012},
month = {11}
}