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タイトル: | NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir. |
著者: | Furukawa, Ayako https://orcid.org/0000-0002-7339-4632 (unconfirmed) Okamura, Hideyasu Morishita, Ryo Matsunaga, Satoko Kobayashi, Naohiro Ikegami, Takahisa Kodaki, Tsutomu Takaori-Kondo, Akifumi Ryo, Akihide Nagata, Takashi https://orcid.org/0000-0002-3733-2709 (unconfirmed) Katahira, Masato https://orcid.org/0000-0003-0336-7660 (unconfirmed) |
著者名の別形: | 永田, 崇 |
キーワード: | XMRV Protease Cell-free protein synthesis NMR |
発行日: | 24-Aug-2012 |
出版者: | Elsevier Inc. |
誌名: | Biochemical and biophysical research communications |
巻: | 425 |
号: | 2 |
開始ページ: | 284 |
終了ページ: | 289 |
抄録: | Xenotropic murine leukemia virus-related virus (XMRV) is a virus created through recombination of two murine leukemia proviruses under artificial conditions during the passage of human prostate cancer cells in athymic nude mice. The homodimeric protease (PR) of XMRV plays a critical role in the production of functional viral proteins and is a prerequisite for viral replication. We synthesized XMRV PR using the wheat germ cell-free expression system and carried out structural analysis of XMRV PR in a complex with an inhibitor, amprenavir (APV), by means of NMR. Five different combinatorially (15)N-labeled samples were prepared and backbone resonance assignments were made by applying Otting's method, with which the amino acid types of the [(1)H, (15)N] HSQC resonances were automatically identified using the five samples (Wu et al., 2006) [14]. A titration experiment involving APV revealed that one APV molecule binds to one XMRV PR dimer. For many residues, two distinct resonances were observed, which is thought to be due to the structural heterogeneity between the two protomers in the APV:XMRV PR=1:2 complex. PR residues at the interface with APV have been identified on the basis of chemical shift perturbation and identification of the intermolecular NOEs by means of filtered NOE experiments. Interestingly, chemical shift heterogeneity between the two protomers of XMRV PR has been observed not only at the interface with APV but also in regions apart from the interface. This indicates that the structural heterogeneity induced by the asymmetry of the binding of APV to the XMRV PR dimer is transmitted to distant regions. This is in contrast to the case of the APV:HIV-1 PR complex, in which the structural heterogeneity is only localized at the interface. Long-range transmission of the structural change identified for the XMRV PR complex might be utilized for the discovery of a new type of drug. |
著作権等: | © 2012 Elsevier Inc. 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。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/159945 |
DOI(出版社版): | 10.1016/j.bbrc.2012.07.083 |
PubMed ID: | 22842568 |
出現コレクション: | 学術雑誌掲載論文等 |
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