Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
Abstract
High-resolution structural data of protein inhibitor complexes are the key to
rational drug design. Synchrotron radiation allows for atomic resolutions but is
frequently accompanied by radiation damage to protein complexes. In this study a
human aldose reductase mutant complexed with a bromine-substituted inhibitor was
determined to atomic resolution [Protein Data Bank (PDB) code 3onc]. Though the
radiation dose was moderate, a selective disruption of a bromine-inhibitor bond
during the experiment was observed while the protein appears unaffected. A
covalent bond to bromine is cleaved and the displaced atom is not scattered
throughout the crystal but can most likely be assigned as a bromide to an
additional difference electron density peak observed in the structure. The
bromide relocates to an adjacent unoccupied site where promising interactions to
protein residues stabilize its position. These findings were verified by a
second similar structure determined with considerably higher radiation dose (PDB
code 3onb).
