TY - JOUR
T1 - Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase
AU - Ealy, Julie B.
AU - Sudol, Malgorzata
AU - Krzeminski, Jacek
AU - Amin, Shantu
AU - Katzman, Michael
N1 - Funding Information:
This work was supported by Public Health Service grant R21AI075929 from the Microbicide Innovation Program of the Office of Women's Health and National Institute of Allergy and Infectious Diseases (to MK) and an American Recovery and Reinvestment Act Administrative Supplement Providing Summer Research Experiences for Students and Science Educators (to MK to support JBE), by the Penn State Hershey Cancer Institute (to MK), and by a Penn State University Research Collaboration Fellowship (to JBE and MK). Some early experiments were supported by the G. Harold and Leila Y. Mathers Charitable Foundation (to MK). We thank Amy Harper and Matthew Nowak for assistance with early work on this project and Shen-Shu Sung for reviewing the data.
PY - 2012/11/10
Y1 - 2012/11/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.virol.2012.07.022
DO - 10.1016/j.virol.2012.07.022
M3 - Article
C2 - 22910593
AN - SCOPUS:84866182288
SN - 0042-6822
VL - 433
SP - 149
EP - 156
JO - Virology
JF - Virology
IS - 1
ER -
