3ONB

Bond breakage and relocation of a covalently bound bromine of IDD594 in a complex with hAR T113A mutant after extensive radiation dose

Summary for 3ONB

• Entry DOI: 10.2210/pdb3onb/pdb
• Related: 1US0 3LBO 3LD5 3LQL 3ONC
• Descriptor: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, IDD594, ... (6 entities in total)
• Functional Keywords: radiation damage, t113a mutant, tim barrel, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 37168.79

Authors

Koch, C.,Heine, A.,Klebe, G. (deposition date: 2010-08-28, release date: 2011-08-17, Last modification date: 2024-03-20)

Primary citation

Koch, C.,Heine, A.,Klebe, G.
Radiation damage reveals promising interaction position
J.SYNCHROTRON RADIAT., 18:782-789, 2011

PubMed 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).

PubMed: 21862860
DOI: 10.1107/S0909049511027920

Experimental method

X-RAY DIFFRACTION (1.45 Å)