title: Indirect readout of the trp-repressor-operator complex by B-DNA's backbone conformation transitions.
abstract: Although the trp-repressor-operator complex is one of the best studied transcriptional controlling systems, some questions regarding the specific recognition of the operator by the repressor remain. We performed a 2.35 ns long molecular dynamics simulation to clarify the influence of the two B-DNA backbone conformational substates B(I) and B(II) on complexation. The trp-repressor-operator is an ideal biological system for this study because experimental results have already figured out that the interaction between the internucleotide phosphates and the protein is essential for the formation of the high affinity complex. Our simulation supports these results, but more important it shows a strong correlation between the B(I)/B(II) phosphate substate and the number of interactions with this phosphate. In particular the B(I) <==> B(II) transitions occur synchronous to hydrogen bond breaking or formation. To the best of our knowledge, this was observed for the first time. Thus, we conclude that the sequence specific B(I)/B(II) behavior contributes via indirect readout to sequence specific recognition. These results have implication for the design of transcription-controlling drugs in view of the recently published influence of minor groove binders on the B(I)/B(II) pattern. The simulation also agrees with crystallographically observed hydration sites. This is consistent with experimental results and indicates the correctness of the model used.
authors.affiliation: Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wellenzohn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Flader
authors.forename: Rudolf H
authors.initials: RH
authors.lastname: Winger
authors.forename: Andreas
authors.initials: A
authors.lastname: Hallbrucker
authors.forename: Erwin
authors.initials: E
authors.lastname: Mayer
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Liedl
mesh_terms: D001426:Bacterial Proteins; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009875:Operator Regions, Genetic; D010100:Oxygen / Q000737:chemistry; D012097:Repressor Proteins / Q000737:chemistry*; D029968:Escherichia coli Proteins
chemical_list: D001426:Bacterial Proteins; D004247:DNA; D010100:Oxygen; D012097:Repressor Proteins; C027190:TRPR protein, E coli; D029968:Escherichia coli Proteins