schliessen

Filtern

 

Bibliotheken

Characterizing the protonation state of cytosine in transient G·C Hoogsteen base pairs in duplex DNA.

G·C Hoogsteen base pairs can form transiently in duplex DNA and play important roles in DNA recognition, replication, and repair. G·C Hoogsteen base pairs are thought to be stabilized by protonation of cytosine N3, which affords a second key hydrogen bond, but experimental evidence for this is spars... Full description

Journal Title: Journal of the American Chemical Society May 8, 2013, Vol.135(18), pp.6766-6769
Main Author: Nikolova, Evgenia N
Other Authors: Goh, Garrett B , Brooks, Charles L , Al-Hashimi, Hashim M
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
ID: E-ISSN: 1520-5126 ; DOI: 10.1021/ja400994e
Link: http://search.proquest.com/docview/1349702670/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1349702670
title: Characterizing the protonation state of cytosine in transient G·C Hoogsteen base pairs in duplex DNA.
format: Article
creator:
  • Nikolova, Evgenia N
  • Goh, Garrett B
  • Brooks, Charles L
  • Al-Hashimi, Hashim M
subjects:
  • Base Pairing–Chemistry
  • Crystallography, X-Ray–Chemistry
  • Cytosine–Chemistry
  • DNA–Chemistry
  • Magnetic Resonance Spectroscopy–Chemistry
  • Molecular Dynamics Simulation–Chemistry
  • Nucleic Acid Conformation–Chemistry
  • Protons–Chemistry
  • Protons
  • Cytosine
  • DNA
ispartof: Journal of the American Chemical Society, May 8, 2013, Vol.135(18), pp.6766-6769
description: G·C Hoogsteen base pairs can form transiently in duplex DNA and play important roles in DNA recognition, replication, and repair. G·C Hoogsteen base pairs are thought to be stabilized by protonation of cytosine N3, which affords a second key hydrogen bond, but experimental evidence for this is sparse because the proton cannot be directly visualized by X-ray crystallography and nuclear magnetic resonance spectroscopy. Here, we combine NMR and constant pH molecular dynamics simulations to directly investigate the pKa of cytosine N3 in a chemically trapped N1-methyl-G·C Hoogsteen base pair within duplex DNA. Analysis of NMR chemical shift perturbations and NOESY data as a function of pH revealed that cytosine deprotonation is coupled to a syn-to-anti transition in N1-methyl-G, which results in a distorted Watson-Crick geometry at pH >9. A four-state analysis of the pH titration profiles yields a lower bound pKa estimate of 7.2 ± 0.1 for the G·C Hoogsteen base pair, which is in good agreement with the pKa value (7.1 ± 0.1) calculated independently using constant pH MD simulations. Based on these results and pH-dependent NMR relaxation dispersion measurements, we estimate that under physiological pH (pH 7-8), G·C Hoogsteen base pairs in naked DNA have a population of 0.02-0.002%, as compared to 0.4% for A·T Hoogsteen base pairs, and likely exist primarily as protonated species.
language: eng
source:
identifier: E-ISSN: 1520-5126 ; DOI: 10.1021/ja400994e
fulltext: fulltext
issn:
  • 15205126
  • 1520-5126
url: Link


@attributes
ID879590898
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1349702670
sourceidproquest
recordidTN_proquest1349702670
sourcesystemPC
pqid1349702670
galeid334202279
display
typearticle
titleCharacterizing the protonation state of cytosine in transient G·C Hoogsteen base pairs in duplex DNA.
creatorNikolova, Evgenia N ; Goh, Garrett B ; Brooks, Charles L ; Al-Hashimi, Hashim M
contributorNikolova, Evgenia N (correspondence author) ; Nikolova, Evgenia N (record owner)
ispartofJournal of the American Chemical Society, May 8, 2013, Vol.135(18), pp.6766-6769
identifierE-ISSN: 1520-5126 ; DOI: 10.1021/ja400994e
subjectBase Pairing–Chemistry ; Crystallography, X-Ray–Chemistry ; Cytosine–Chemistry ; DNA–Chemistry ; Magnetic Resonance Spectroscopy–Chemistry ; Molecular Dynamics Simulation–Chemistry ; Nucleic Acid Conformation–Chemistry ; Protons–Chemistry ; Protons ; Cytosine ; DNA
languageeng
source
descriptionG·C Hoogsteen base pairs can form transiently in duplex DNA and play important roles in DNA recognition, replication, and repair. G·C Hoogsteen base pairs are thought to be stabilized by protonation of cytosine N3, which affords a second key hydrogen bond, but experimental evidence for this is sparse because the proton cannot be directly visualized by X-ray crystallography and nuclear magnetic resonance spectroscopy. Here, we combine NMR and constant pH molecular dynamics simulations to directly investigate the pKa of cytosine N3 in a chemically trapped N1-methyl-G·C Hoogsteen base pair within duplex DNA. Analysis of NMR chemical shift perturbations and NOESY data as a function of pH revealed that cytosine deprotonation is coupled to a syn-to-anti transition in N1-methyl-G, which results in a distorted Watson-Crick geometry at pH >9. A four-state analysis of the pH titration profiles yields a lower bound pKa estimate of 7.2 ± 0.1 for the G·C Hoogsteen base pair, which is in good agreement with the pKa value (7.1 ± 0.1) calculated independently using constant pH MD simulations. Based on these results and pH-dependent NMR relaxation dispersion measurements, we estimate that under physiological pH (pH 7-8), G·C Hoogsteen base pairs in naked DNA have a population of 0.02-0.002%, as compared to 0.4% for A·T Hoogsteen base pairs, and likely exist primarily as protonated species.
version4
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1349702670/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Nikolova, Evgenia N
1Goh, Garrett B
2Brooks, Charles L
3Al-Hashimi, Hashim M
titleCharacterizing the protonation state of cytosine in transient G·C Hoogsteen base pairs in duplex DNA.
subject
0Base Pairing–Chemistry
1Crystallography, X-Ray–Chemistry
2Cytosine–Chemistry
3DNA–Chemistry
4Magnetic Resonance Spectroscopy–Chemistry
5Molecular Dynamics Simulation–Chemistry
6Nucleic Acid Conformation–Chemistry
7Protons–Chemistry
8Protons
9Cytosine
10DNA
general
0English
110.1021/ja400994e
2MEDLINE (ProQuest)
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Biological Science Database
7Natural Science Collection
8SciTech Premium Collection
9Health Research Premium Collection
10Health Research Premium Collection (Alumni edition)
11Biological Science Index (ProQuest)
sourceidproquest
recordidproquest1349702670
issn
015205126
11520-5126
rsrctypearticle
creationdate2013
addtitleJournal of the American Chemical Society
searchscope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
scope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
lsr43
01007527false
11007944false
21009130false
310000004false
410000038false
510000050false
610000120false
710000159false
810000238false
910000253false
1010000260false
1110000270false
1210000271false
1310000302false
1410000350false
contributorNikolova, Evgenia N
startdate20130508
enddate20130508
citationpf 6766 pt 6769 vol 135 issue 18
lsr30VSR-Enriched:[description, galeid, issn, pqid]
sort
titleCharacterizing the protonation state of cytosine in transient G·C Hoogsteen base pairs in duplex DNA.
authorNikolova, Evgenia N ; Goh, Garrett B ; Brooks, Charles L ; Al-Hashimi, Hashim M
creationdate20130508
lso0120130508
facets
frbrgroupid4590658045283960080
frbrtype5
newrecords20181218
languageeng
creationdate2013
topic
0Base Pairing–Chemistry
1Crystallography, X-Ray–Chemistry
2Cytosine–Chemistry
3DNA–Chemistry
4Magnetic Resonance Spectroscopy–Chemistry
5Molecular Dynamics Simulation–Chemistry
6Nucleic Acid Conformation–Chemistry
7Protons–Chemistry
8Protons
9Cytosine
10DNA
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
9Biological Science Index (ProQuest)
prefilterarticles
rsrctypearticles
creatorcontrib
0Nikolova, Evgenia N
1Goh, Garrett B
2Brooks, Charles L
3Al-Hashimi, Hashim M
jtitleJournal of the American Chemical Society
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Nikolova
1Goh
2Brooks
3Al-Hashimi
aufirst
0Evgenia N
1Garrett B
2Charles L
3Hashim M
au
0Nikolova, Evgenia N
1Goh, Garrett B
2Brooks, Charles L
3Al-Hashimi, Hashim M
addauNikolova, Evgenia N
atitleCharacterizing the protonation state of cytosine in transient G·C Hoogsteen base pairs in duplex DNA.
jtitleJournal of the American Chemical Society
risdate20130508
volume135
issue18
spage6766
epage6769
pages6766-6769
eissn1520-5126
formatjournal
genrearticle
ristypeJOUR
doi10.1021/ja400994e
urlhttp://search.proquest.com/docview/1349702670/
issn00027863
date2013-05-08