Ionization states of the catalytic residues in HIV-1 protease

Smith, Ross, Brereton, Ian M., Chai, Richard Y. and Kent, Stephen B. H. (1996) Ionization states of the catalytic residues in HIV-1 protease. Nature Structural Biology, 3 11: 946-950. doi:10.1038/nsb1196-946

Author Smith, Ross
Brereton, Ian M.
Chai, Richard Y.
Kent, Stephen B. H.
Title Ionization states of the catalytic residues in HIV-1 protease
Journal name Nature Structural Biology   Check publisher's open access policy
ISSN 1545-9993
Publication date 1996
Sub-type Article (original research)
DOI 10.1038/nsb1196-946
Volume 3
Issue 11
Start page 946
End page 950
Total pages 5
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Abstract Chemical synthesis was used to prepare the HIV-1 protease specifically 13C-labelled in the catalytically essential Asp 25 in each monomer. The NMR chemical shift of the 13C-enriched homodimeric enzyme was measured in the presence of the inhibitor pepstatin, a mimic of the tetrahedral intermediate formed in enzyme catalysis. In this complex, the catalytic carboxyls do not titrate in the pH range where the enzyme is active; throughout the range pH 2.5-6.5, one Asp 25 side chain is protonated and the other deprotonated. By contrast, in the absence of inhibitor the two Asp side chains are chemically equivalent and both deprotonated at pH 6, the optimum for enzymatic activity. These direct observations of the chemical properties of the catalytic apparatus of the enzyme provide concrete information on which to base the design of improved HIV-1 protease inhibitors.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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