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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
Okamura, Hideyasu
Morishita, Ryo
Matsunaga, Satoko
Kobayashi, Naohiro
Ikegami, Takahisa
Kodaki, Tsutomu  kyouindb  KAKEN_id
Takaori-Kondo, Akifumi
Ryo, Akihide
Nagata, Takashi  kyouindb  KAKEN_id
Katahira, Masato  kyouindb  KAKEN_id
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.
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/2433/159945
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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