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Title: Quantitative analysis of location- and sequence-dependent deamination by APOBEC3G using real-time NMR spectroscopy.
Authors: Furukawa, Ayako
Sugase, Kenji  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-8623-7743 (unconfirmed)
Morishita, Ryo
Nagata, Takashi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-3733-2709 (unconfirmed)
Kodaki, Tsutomu  kyouindb  KAKEN_id
Takaori-Kondo, Akifumi
Ryo, Akihide
Katahira, Masato  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-0336-7660 (unconfirmed)
Author's alias: 古川, 亜矢子
片平, 正人
Keywords: deamination
DNA
enzyme kinetics
quantitative analysis
NMR spectroscopy
Issue Date: 29-Jan-2014
Publisher: wiley
Journal title: Angewandte Chemie
Volume: 53
Issue: 9
Start page: 2349
End page: 2352
Abstract: The human antiretroviral factor APOBEC3G (A3G) deaminates the newly synthesized minus strand of the human immunodeficiency virus 1 (HIV-1), which results in the abolition of the infectivity of virus-infectivity-factor (Vif)-deficient HIV-1 strains.1-6 A unique property of A3G is that it deaminates a CCC hot spot that is located close to the 5' end more effectively than one that is less close to the 5' end. However, the mechanism of this process is elusive as it includes nonspecific binding of A3G to DNA and sliding of A3G along the DNA strand. Therefore, this process cannot be analyzed by existing methods using the Michaelis-Menten theory. A new real-time NMR method has been developed to examine the nonspecific binding and the sliding processes explicitly, and it was applied to the analysis of the deamination by A3G. As a result, the location-dependent deamination can be explained by a difference in the catalytic rates that depend on the direction of the approach of A3G to the target cytidine. Real-time NMR experiments also showed that A3G deaminates CCCC tandem hotspots with little redundancy, which suggests that A3G efficiently mutates many CCC hotspots that are scattered throughout the HIV-1 genome.
Description: NMR法を用いた実時間追跡で抗エイズウイルス酵素反応の定量解析に成功 -新規抗エイズウイルス薬創製に期待-. 京都大学プレスリリース. 2014-01-29.
Rights: This is the peer reviewed version of the following article: Furukawa, A., Sugase, K., Morishita, R., Nagata, T., Kodaki, T., Takaori-Kondo, A., Ryo, A. and Katahira, M. (2014), Quantitative Analysis of Location- and Sequence-Dependent Deamination by APOBEC3G Using Real-Time NMR Spectroscopy. Angew. Chem. Int. Ed., 53: 2349–2352, which has been published in final form at http://dx.doi.org/10.1002/anie.201309940. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/199659
DOI(Published Version): 10.1002/anie.201309940
PubMed ID: 24478136
Related Link: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2013_1/140108_2.htm
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