Platinum-DNA interstrand crosslinks: Molecular determinants of
bending and unwinding of the double helix.

J 2012

Platinum-DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix.

SUCHÁNKOVÁ, Tereza, Karel KUBÍČEK, Jana KAŠPÁRKOVÁ, Viktor BRABEC, Jiří KOZELKA et. al.

Basic information

Original name

Platinum-DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix.

Authors

SUCHÁNKOVÁ, Tereza (203 Czech Republic), Karel KUBÍČEK (203 Czech Republic, belonging to the institution), Jana KAŠPÁRKOVÁ (203 Czech Republic), Viktor BRABEC (203 Czech Republic, belonging to the institution) and Jiří KOZELKA (250 France, guarantor, belonging to the institution)

Edition

Journal of Inorganic Biochemistry, New York, USA, Elsevier Science Inc, 2012, 0162-0134

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.197

RIV identification code

RIV/00216224:14310/12:00057206

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.jinorgbio.2011.09.025

UT WoS

000302205600010

Keywords in English

Anticancer drugs; Cisplatin; DNA binding; Interstrand crosslinks; Lone pair-pi interactions; Molecular dynamics simulations

Abstract

V originále

Platinum diamine complexes are able to crosslink the guanines of d(GC)2 dinucleotides within double-stranded DNA. The interstrand crosslink thus formed causes a bend of the double helix toward the minor groove and the helical sense changes locally to left-handed, resulting in a considerable unwinding. The bend and unwinding angles have been shown to depend on the platinum ligands. Here, we have used molecular dynamics simulations to investigate the DNA 20-mer d(C1T2C3T4C5C6T7T8G*9C10T11C12T13C14C15T16T17C18T19C20)-d(G21A22G23A24A25G26G27A28G29A30G*31C32A33A34G35G36A37G38A39G40) with the G* guanines crosslinked by cis-Pt(NH3)22+, Pt(R,R-DACH)2+, or Pt(S,S-DACH)2+. Previous investigations on cisplatin interstrand adducts indicated that the structure is similar in solid state and in solution; thus, we used the reported X-ray structure of a cisplatin adduct as a starting model. Replacing in the MD-relaxed model for the DNA duplex crosslinked with cis-Pt(NH3)22+ the two NH3 platinum ligands by R,R-DACH or S,S-DACH led to clashes between the DACH residue and the deoxyribose of C12. Confrontation of MD-derived models with gel shift measurements suggested that these clashes are avoided differently in the adducts of Pt(R,R-DACH)2+versus Pt(S,S-DACH)2+. The R,R-isomer avoids the clash by untwisting the T11/A30–C12/G29 step, thus increasing the global unwinding. In contrast, the S,S-isomer modifies the shift and slide parameters of this step, which dislocates the helical axis and enhances the bend angle. The clash that leads to the differentiation of the structures as a function of the diamine ligand is related to a hydrogen bond between the platinum complex and the T11 base and could be characteristic of interstrand crosslinks at d(pyG*Cpy)-d(puG*Cpu) sequences.

Links

GP202/08/P416, research and development project

Name: Studium interakce mezi cisplatinovanou G/T "mismatched" DNA s proteinem MutS pomocí NMR

Investor: Czech Science Foundation, NMR study of interaction of cisplatined G/T mismatched DNA substrate with protein MutS

MUNI/A/1046/2009, interní kód MU

Name: Biofyzikální výzkum struktur a funkcí biomolekul (Acronym: BVSFB)

Investor: Masaryk University, Category A

Citovat

SUCHÁNKOVÁ, Tereza, Karel KUBÍČEK, Jana KAŠPÁRKOVÁ, Viktor BRABEC and Jiří KOZELKA. Platinum-DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix. Journal of Inorganic Biochemistry. New York, USA: Elsevier Science Inc, 2012, vol. 108, No 1, p. 69-79. ISSN 0162-0134. Available from: https://dx.doi.org/10.1016/j.jinorgbio.2011.09.025.

@article{955330,
   author = {Suchánková, Tereza and Kubíček, Karel and Kašpárková, Jana and Brabec, Viktor and Kozelka, Jiří},
   article_location = {New York, USA},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.jinorgbio.2011.09.025},
   keywords = {Anticancer drugs; Cisplatin; DNA binding; Interstrand crosslinks; Lone pair-pi interactions; Molecular dynamics simulations},
   language = {eng},
   issn = {0162-0134},
   journal = {Journal of Inorganic Biochemistry},
   title = {Platinum-DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix.},
   volume = {108},
   year = {2012}
}

TY  - JOUR
ID  - 955330
AU  - Suchánková, Tereza - Kubíček, Karel - Kašpárková, Jana - Brabec, Viktor - Kozelka, Jiří
PY  - 2012
TI  - Platinum-DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix.
JF  - Journal of Inorganic Biochemistry
VL  - 108
IS  - 1
SP  - 69-79
EP  - 69-79
PB  - Elsevier Science Inc
SN  - 01620134
KW  - Anticancer drugs
KW  - Cisplatin
KW  - DNA binding
KW  - Interstrand crosslinks
KW  - Lone pair-pi interactions
KW  - Molecular dynamics simulations
N2  - Platinum diamine complexes are able to crosslink the guanines of d(GC)2 dinucleotides within double-stranded DNA. The interstrand crosslink thus formed causes a bend of the double helix toward the minor groove and the helical sense changes locally to left-handed, resulting in a considerable unwinding. The bend and unwinding angles have been shown to depend on the platinum ligands. Here, we have used molecular dynamics simulations to investigate the DNA 20-mer d(C1T2C3T4C5C6T7T8G*9C10T11C12T13C14C15T16T17C18T19C20)-d(G21A22G23A24A25G26G27A28G29A30G*31C32A33A34G35G36A37G38A39G40) with the G* guanines crosslinked by cis-Pt(NH3)22+, Pt(R,R-DACH)2+, or Pt(S,S-DACH)2+. Previous investigations on cisplatin interstrand adducts indicated that the structure is similar in solid state and in solution; thus, we used the reported X-ray structure of a cisplatin adduct as a starting model. Replacing in the MD-relaxed model for the DNA duplex crosslinked with cis-Pt(NH3)22+ the two NH3 platinum ligands by R,R-DACH or S,S-DACH led to clashes between the DACH residue and the deoxyribose of C12. Confrontation of MD-derived models with gel shift measurements suggested that these clashes are avoided differently in the adducts of Pt(R,R-DACH)2+versus Pt(S,S-DACH)2+. The R,R-isomer avoids the clash by untwisting the T11/A30–C12/G29 step, thus increasing the global unwinding. In contrast, the S,S-isomer modifies the shift and slide parameters of this step, which dislocates the helical axis and enhances the bend angle. The clash that leads to the differentiation of the structures as a function of the diamine ligand is related to a hydrogen bond between the platinum complex and the T11 base and could be characteristic of interstrand crosslinks at d(pyG*Cpy)-d(puG*Cpu) sequences.
ER  -

SUCHÁNKOVÁ, Tereza, Karel KUBÍČEK, Jana KAŠPÁRKOVÁ, Viktor BRABEC and Jiří KOZELKA. Platinum-DNA interstrand crosslinks: Molecular determinants of bending and unwinding of the double helix. \textit{Journal of Inorganic Biochemistry}. New York, USA: Elsevier Science Inc, 2012, vol.~108, No~1, p.~69-79. ISSN~0162-0134. Available from: https://dx.doi.org/10.1016/j.jinorgbio.2011.09.025.

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