Ionization states of the catalytic residues in hiv-1 protease

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. Access through your institution Buy or subscribe This is a

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Biochemistry, University of Queensland, Qld, 4072, Australia Ross Smith * Center for Magnetic Resonance, University of Queensland, Qld, 4072, Australia Ian M. Brereton * The Scripps

Research Institute, La Jolla, California, 92037, USA Richard Y. Chai & Stephen B.H. Kent Authors * Ross Smith View author publications You can also search for this author inPubMed Google

Scholar * Ian M. Brereton View author publications You can also search for this author inPubMed Google Scholar * Richard Y. Chai View author publications You can also search for this author

inPubMed Google Scholar * Stephen B.H. Kent View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS

ARTICLE CITE THIS ARTICLE Smith, R., Brereton, I., Chai, R. _et al._ Ionization states of the catalytic residues in HIV-1 protease. _Nat Struct Mol Biol_ 3, 946–950 (1996).

https://doi.org/10.1038/nsb1196-946 Download citation * Received: 20 May 1996 * Accepted: 20 September 1996 * Issue Date: 01 November 1996 * DOI: https://doi.org/10.1038/nsb1196-946 SHARE

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