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Title: Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor

Abstract

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.

Authors:
 [1];  [2];  [3];  [2];  [1]
  1. Spallation Neutron Source, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831 (United States)
  2. 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)
  3. Bioscience Division, Mailstop M888, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)
Publication Date:
OSTI Identifier:
22360443
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section F
Additional Journal Information:
Journal Volume: 63; Journal 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); Journal ID: ISSN 1744-3091
Country of Publication:
United Kingdom
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; ATOMS; CRYSTALS; GLYCOLS; NEUTRON DIFFRACTION; NEUTRONS; RESOLUTION; SOLVENTS; SYNCHROTRONS; X-RAY DIFFRACTION

Citation Formats

Tuan, Han-Fang, Erskine, Peter, Langan, Paul, Department of Chemistry, University of Toledo, Toledo, OH 53606, Cooper, Jon, Coates, Leighton, and Department of Chemistry, University of Toledo, Toledo, OH 53606. Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor. United Kingdom: N. p., 2007. Web. doi:10.1107/S1744309107061283.
Tuan, Han-Fang, Erskine, Peter, Langan, Paul, Department of Chemistry, University of Toledo, Toledo, OH 53606, Cooper, Jon, Coates, Leighton, & Department of Chemistry, University of Toledo, Toledo, OH 53606. Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor. United Kingdom. https://doi.org/10.1107/S1744309107061283
Tuan, Han-Fang, Erskine, Peter, Langan, Paul, Department of Chemistry, University of Toledo, Toledo, OH 53606, Cooper, Jon, Coates, Leighton, and Department of Chemistry, University of Toledo, Toledo, OH 53606. 2007. "Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor". United Kingdom. https://doi.org/10.1107/S1744309107061283.
@article{osti_22360443,
title = {Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor},
author = {Tuan, Han-Fang and Erskine, Peter and Langan, Paul and Department of Chemistry, University of Toledo, Toledo, OH 53606 and Cooper, Jon and Coates, Leighton and Department of Chemistry, University of Toledo, Toledo, OH 53606},
abstractNote = {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.},
doi = {10.1107/S1744309107061283},
url = {https://www.osti.gov/biblio/22360443}, journal = {Acta Crystallographica. Section F},
issn = {1744-3091},
number = Pt 12,
volume = 63,
place = {United Kingdom},
year = {Sat Dec 01 00:00:00 EST 2007},
month = {Sat Dec 01 00:00:00 EST 2007}
}