Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
A Mechanism to Understand the Dynamics of Tryptophan Repressor
Trp repressor was an early paradigm for understanding DNA binding, but presented many still-unsolved mysteries, including the non-cooperative binding of L-tryptophan, the presence of a buried water layer at the DNA interface, and extensive local dynamics in the DNA-binding domains. The crystal structure of a temperature-sensitive mutant of E. coli TrpR now suggests a mechanism for the dynamics of the wildtype protein. One subunit of the mutant crystal structure shows an extensive rearrangement in the DNA-binding region, whereas the other subunit is in the wildtype conformation. Comparison with isomorphous wildtype crystals reveals that the distorted conformation is not an artifact of crystallization. Reinvestigation of NMR data for the mutant shows that this conformation can explain NOEs that are not accounted for by a wildtype-like structure. A survey of the extensive NMR data on the wildtype protein reveals that many puzzling features in the dynamics of the protein could also be explained by the presence of this alternative conformation. This hypothesis is presently being tested by NMR and molecular dynamics simulations.