Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor.
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 A) 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.
Tuan
Han-Fang
HF
Spallation Neutron Source, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831, USA.
Erskine
Peter
P
Langan
Paul
P
Cooper
Jon
J
Coates
Leighton
L
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003460:Crystallization; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry*; D033363:Neutron Diffraction; D011485:Protein Binding; D014961:X-Ray Diffraction
D004791:Enzyme Inhibitors; D007093:Imidazoles; D009025:Morpholines; C480723:PD-135,040; D016282:Aspartic Acid Endopeptidases; C042466:Endothia aspartic proteinase