Effects of Cisplatin binding to DNA on the dynamics of the E. Coli MutS dimer.
MSH proteins are capable of recognizing damage in DNA due to a common chemotheraputic, cisplatin, and consequently participate in the initiation of cell death pathways. While previous studies have used computational modeling and cell biology to demonstrate that there are specific structural responses to cisplatin damage that are critical to the initiation of apoptosis, this study demonstrates that there are also specific dynamical changes that are also associated with cisplatin binding. These changes further distinguish the undamaged MutS/DNA complex from the damaged MutS/DNA complex and suggest that there are dynamical aspects to the response of MSH proteins to the binding of DNA damaged by therapeutics; consideration of these responses may influence further drug design and development.
Salsbury
F R
FR
Wake Forest University, Department of Physics, Winston-Salem, NC 27106 USA. salsbufr@wfu.edu
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D002945:Cisplatin / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D051719:MutS DNA Mismatch-Binding Protein / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli; D002945:Cisplatin