Functional Characterization of the Protease of Human Endogenous Retrovirus, K10: Can It Complement HIV-1 Protease?
详细信息 查看全文
- 作者：Eric M. Towler ; Sergei V. Gulnik ; T. N. Bhat ; Dong Xie ; Elena Gustschina ; Terry R. Sumpter ; Nicole Robertson ; Christopher Jones ; Marlies Sauter ; Nikolaus Mueller-Lantzsch ; Christine Debouck ; and John
- 刊名：Biochemistry
- 出版年：1998
- 出版时间：December 8, 1998
- 年：1998
- 卷：37
- 期：49
- 页码：17137 - 17144
- 全文大小：134K
- 年卷期：v.37,no.49(December 8, 1998)
- ISSN：1520-4995
文摘
To investigate the biochemical properties of the protease encoded by the human endogenousretrovirus, K10 (HERV-K), 213 amino acids of the 3'-end of the HERV-K protease (PR) open readingframe were expressed in Escherichia coli. Autocatalytic cleavage of the expressed polypeptide resultedin an 18.2 kDa protein which was shown to be proteolytically active against a fluorogenic peptide usedas a substrate for HIV-1 protease. On the basis of sequence homology and molecular modeling, the 106N-terminal amino acids of HERV-K PR were predicted to comprise a retroviral protease core domain.An 11.6 kDa protein corresponding to this region was expressed and shown to be a fully functional enzyme.The 11.6 kDa domain of HERV-K PR is unusually stable over a wide pH range, exhibits optimal catalyticactivity between pH 4.0 and 5.0, and exists as a dimer at pH 7.0 with a Kd of 50 
M. Like HIV-1 PR, theHERV-K PR core domain is activated by high salt concentrations and processes HIV-1 matrix-capsidpolyprotein at the authentic HIV-1 PR recognition site. However, both the 18.2 and 11.6 kDa forms ofHERV-K PR were highly resistant to a number of clinically useful HIV-1 PR inhibitors, including ritonavir,indinavir, and saquinavir. This raises the possibility that HERV-K PR may complement HIV-1 PR duringinfection, and could have implications for protease inhibitor therapy and drug resistance.
M. Like HIV-1 PR, theHERV-K PR core domain is activated by high salt concentrations and processes HIV-1 matrix-capsidpolyprotein at the authentic HIV-1 PR recognition site. However, both the 18.2 and 11.6 kDa forms ofHERV-K PR were highly resistant to a number of clinically useful HIV-1 PR inhibitors, including ritonavir,indinavir, and saquinavir. This raises the possibility that HERV-K PR may complement HIV-1 PR duringinfection, and could have implications for protease inhibitor therapy and drug resistance.