論文

査読有り
2012年8月

NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Ayako Furukawa
  • Hideyasu Okamura
  • Ryo Morishita
  • Satoko Matsunaga
  • Naohiro Kobayashi
  • Takahisa Ikegami
  • Tsutomu Kodaki
  • Akifumi Takaori-Kondo
  • Akihide Ryo
  • Takashi Nagata
  • Masato Katahira
  • 全て表示

425
2
開始ページ
284
終了ページ
289
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2012.07.083
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

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 N-15-labeled samples were prepared and backbone resonance assignments were made by applying Otting's method, with which the amino acid types of the [H-1, N-15] 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. (c) 2012 Elsevier Inc. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2012.07.083
J-GLOBAL
https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201202279852426790
CiNii Articles
http://ci.nii.ac.jp/naid/120004873605
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22842568
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000308384400028&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.bbrc.2012.07.083
  • ISSN : 0006-291X
  • eISSN : 1090-2104
  • J-Global ID : 201202279852426790
  • CiNii Articles ID : 120004873605
  • PubMed ID : 22842568
  • Web of Science ID : WOS:000308384400028

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