A detailed interpretation of OH radical footprints in a TBP-DNA complex reveals the role of dynamics in mechanism of sequence-specific binding

Nina Pastor, Harel Weinstein, Elizabeth Jamison, Michael D. Brenowitz

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

The hydroxyl radical footprint of the TATA-binding protein (TBP) bound to the high-affinity sequence TATAAAAG of the adenovirus 2 major late promoter has been quantitatively compared to a 2 ns molecular dynamics simulation of the complex in aqueous solution at room temperature using the CHARMM23 potential. The nucleotide-by-nucleotide analysis of the TBP-TATA hydroxyl radical footprint correlates with the solvent-accessible surface calculated from the dynamics simulation. The results suggest that local reactivity towards OH radicals results from the interplay between the local DNA geometry imposed by TBP binding, and the dynamics of the side-chains contacting the sugar hydrogen atoms. Analysis of the dynamics suggests that, over time, TBP forms stable interactions with the sugar-phosphate backbone through multiple contacts to different partners. This mechanism results in an enthalpic advantage to complex formation at a low entropic cost. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)55-68
Number of pages14
JournalJournal of Molecular Biology
Volume304
Issue number1
DOIs
StatePublished - Nov 17 2000

Fingerprint

TATA-Box Binding Protein
DNA
Hydroxyl Radical
Nucleotides
Sugar Phosphates
Molecular Dynamics Simulation
Protein Binding
Adenoviridae
Hydrogen
Costs and Cost Analysis
Temperature

Keywords

  • Entropy/enthalpy compensation
  • Molecular dynamics
  • Transcription

ASJC Scopus subject areas

  • Virology

Cite this

A detailed interpretation of OH radical footprints in a TBP-DNA complex reveals the role of dynamics in mechanism of sequence-specific binding. / Pastor, Nina; Weinstein, Harel; Jamison, Elizabeth; Brenowitz, Michael D.

In: Journal of Molecular Biology, Vol. 304, No. 1, 17.11.2000, p. 55-68.

Research output: Contribution to journalArticle

@article{5f047d22d0ed44a9a6efa003ca457341,
title = "A detailed interpretation of OH radical footprints in a TBP-DNA complex reveals the role of dynamics in mechanism of sequence-specific binding",
abstract = "The hydroxyl radical footprint of the TATA-binding protein (TBP) bound to the high-affinity sequence TATAAAAG of the adenovirus 2 major late promoter has been quantitatively compared to a 2 ns molecular dynamics simulation of the complex in aqueous solution at room temperature using the CHARMM23 potential. The nucleotide-by-nucleotide analysis of the TBP-TATA hydroxyl radical footprint correlates with the solvent-accessible surface calculated from the dynamics simulation. The results suggest that local reactivity towards OH radicals results from the interplay between the local DNA geometry imposed by TBP binding, and the dynamics of the side-chains contacting the sugar hydrogen atoms. Analysis of the dynamics suggests that, over time, TBP forms stable interactions with the sugar-phosphate backbone through multiple contacts to different partners. This mechanism results in an enthalpic advantage to complex formation at a low entropic cost. (C) 2000 Academic Press.",
keywords = "Entropy/enthalpy compensation, Molecular dynamics, Transcription",
author = "Nina Pastor and Harel Weinstein and Elizabeth Jamison and Brenowitz, {Michael D.}",
year = "2000",
month = "11",
day = "17",
doi = "10.1006/jmbi.2000.4173",
language = "English (US)",
volume = "304",
pages = "55--68",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - A detailed interpretation of OH radical footprints in a TBP-DNA complex reveals the role of dynamics in mechanism of sequence-specific binding

AU - Pastor, Nina

AU - Weinstein, Harel

AU - Jamison, Elizabeth

AU - Brenowitz, Michael D.

PY - 2000/11/17

Y1 - 2000/11/17

N2 - The hydroxyl radical footprint of the TATA-binding protein (TBP) bound to the high-affinity sequence TATAAAAG of the adenovirus 2 major late promoter has been quantitatively compared to a 2 ns molecular dynamics simulation of the complex in aqueous solution at room temperature using the CHARMM23 potential. The nucleotide-by-nucleotide analysis of the TBP-TATA hydroxyl radical footprint correlates with the solvent-accessible surface calculated from the dynamics simulation. The results suggest that local reactivity towards OH radicals results from the interplay between the local DNA geometry imposed by TBP binding, and the dynamics of the side-chains contacting the sugar hydrogen atoms. Analysis of the dynamics suggests that, over time, TBP forms stable interactions with the sugar-phosphate backbone through multiple contacts to different partners. This mechanism results in an enthalpic advantage to complex formation at a low entropic cost. (C) 2000 Academic Press.

AB - The hydroxyl radical footprint of the TATA-binding protein (TBP) bound to the high-affinity sequence TATAAAAG of the adenovirus 2 major late promoter has been quantitatively compared to a 2 ns molecular dynamics simulation of the complex in aqueous solution at room temperature using the CHARMM23 potential. The nucleotide-by-nucleotide analysis of the TBP-TATA hydroxyl radical footprint correlates with the solvent-accessible surface calculated from the dynamics simulation. The results suggest that local reactivity towards OH radicals results from the interplay between the local DNA geometry imposed by TBP binding, and the dynamics of the side-chains contacting the sugar hydrogen atoms. Analysis of the dynamics suggests that, over time, TBP forms stable interactions with the sugar-phosphate backbone through multiple contacts to different partners. This mechanism results in an enthalpic advantage to complex formation at a low entropic cost. (C) 2000 Academic Press.

KW - Entropy/enthalpy compensation

KW - Molecular dynamics

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=0034680558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034680558&partnerID=8YFLogxK

U2 - 10.1006/jmbi.2000.4173

DO - 10.1006/jmbi.2000.4173

M3 - Article

C2 - 11071810

AN - SCOPUS:0034680558

VL - 304

SP - 55

EP - 68

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 1

ER -