Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor
- Spallation Neutron Source, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831 (United States)
- Laboratory for Protein Crystallography, Centre for Amyloidosis and Acute Phase Proteins, UCL Department of Medicine (Hampstead Campus), Rowland Hill Street, London NW3 2PF (United Kingdom)
- Bioscience Division, Mailstop M888, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)
Three data sets have been collected on endothiapepsin complexed with the gem-diol inhibitor PD-135,040: a high-resolution synchrotron X-ray data set, a room-temperature X-ray data set and a neutron diffraction data set. Until recently, it has been impossible to grow large protein crystals of endothiapepsin with any gem-diol inhibitor that are suitable for neutron diffraction. Endothiapepsin has been cocrystallized with the gem-diol inhibitor PD-135,040 in a low solvent-content (39%) unit cell, which is unprecedented for this enzyme–inhibitor complex and enables ultrahigh-resolution (1.0 Å) X-ray diffraction data to be collected. This atomic resolution X-ray data set will be used to deduce the protonation states of the catalytic aspartate residues. A room-temperature neutron data set has also been collected for joint refinement with a room-temperature X-ray data set in order to locate the H/D atoms at the active site.
- OSTI ID:
- 22360443
- Journal Information:
- Acta Crystallographica. Section F, Vol. 63, Issue Pt 12; Other Information: PMCID: PMC2344097; PMID: 18084100; PUBLISHER-ID: en5271; OAI: oai:pubmedcentral.nih.gov:2344097; Copyright (c) International Union of Crystallography 2007; Country of input: International Atomic Energy Agency (IAEA); ISSN 1744-3091
- Country of Publication:
- United Kingdom
- Language:
- English
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