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Total chemical synthesis of human T-cell leukemia virus type 1 protease via native chemical ligation.


ABSTRACT: Human T-cell leukemia virus 1 (HTLV-1) protease, a member of the aspartic acid protease family, plays critical roles in the pathogenesis of the virus and is an attractive viral target for therapeutic intervention. HTLV-1 protease consists of 125 amino acid residues and functions as a homodimer stabilized in part by a four-stranded beta-sheet comprising the N- and C-termini. Compared with many other viral proteases such as HIV-1 protease, HTLV-1 protease is elongated by an extra 10 amino acid residue "tail" at the C-terminus. The structural and functional role of the extra C-terminal residues in the catalysis of HTLV-1 protease has been a subject of debate for years. Using the native chemical ligation technique pioneered by Kent and coworkers, we chemically synthesized a full-length HTLV protease and a C-terminally truncated form encompassing residues 1-116. Enzyme kinetic analysis using three different peptide substrates indicated that truncation of the C-terminal tail lowered the turnover number of the viral enzyme by a factor of 2 and its catalytic efficiency by roughly 10-fold. Our findings differ from the two extreme views that the C-terminal tail of HTLV-1 protease is either fully dispensable or totally required for enzyme dimerization and/or catalysis.

SUBMITTER: Li C 

PROVIDER: S-EPMC2917242 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Total chemical synthesis of human T-cell leukemia virus type 1 protease via native chemical ligation.

Li Changqing C   Li Xiangqun X   Lu Wuyuan W  

Biopolymers 20100101 4


Human T-cell leukemia virus 1 (HTLV-1) protease, a member of the aspartic acid protease family, plays critical roles in the pathogenesis of the virus and is an attractive viral target for therapeutic intervention. HTLV-1 protease consists of 125 amino acid residues and functions as a homodimer stabilized in part by a four-stranded beta-sheet comprising the N- and C-termini. Compared with many other viral proteases such as HIV-1 protease, HTLV-1 protease is elongated by an extra 10 amino acid res  ...[more]

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