PDBsum entry 3o62

Structural protein/DNA

PDB id: 3o62

Contents

Protein chains

98 a.a. *

80 a.a. *

105 a.a. *

95 a.a. *

84 a.a. *

DNA/RNA

Ligands

CPT

* Residue conservation analysis

PDB id:

3o62

Name:

Structural protein/DNA

Title:

Nucleosome core particle modified with a cisplatin 1,3-cis-{pt(nh3) 2}2+-d(gptpg) intrastrand cross-link

Structure:

Histone h3.2. Chain: a, e. Engineered: yes. Histone h4. Chain: b, f. Engineered: yes. Histone h2a type 1. Chain: c, g. Engineered: yes.

Source:

Xenopus laevis. African clawed frog. Organism_taxid: 8355. Gene: h3.2. Expressed in: escherichia coli. Expression_system_taxid: 562. Clawed frog,common platanna,platanna. Synthetic: yes. Other_details: DNA synthesizer.

Resolution:

3.22Å R-factor: 0.252 R-free: 0.306

Authors:

S.J.Lippard,R.C.Todd

Key ref:

R.C.Todd and S.J.Lippard (2010). Consequences of cisplatin binding on nucleosome structure and dynamics. Chem Biol, 17, 1334-1343. PubMed id: 21168769

Date:

28-Jul-10 Release date: 05-Jan-11

Protein chains

P84233  (H32_XENLA) -  Histone H3.2 from Xenopus laevis

Seq: 136 a.a.

Struc: 98 a.a.*

Protein chain

P62799  (H4_XENLA) -  Histone H4 from Xenopus laevis

Seq: 103 a.a.

Struc: 80 a.a.

Protein chains

P06897  (H2A1_XENLA) -  Histone H2A type 1 from Xenopus laevis

Seq: 130 a.a.

Struc: 105 a.a.*

Protein chains

P02281  (H2B11_XENLA) -  Histone H2B 1.1 from Xenopus laevis

Seq: 126 a.a.

Struc: 95 a.a.*

Protein chain

P62799  (H4_XENLA) -  Histone H4 from Xenopus laevis

Seq: 103 a.a.

Struc: 84 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DNA/RNA chains

A-T-C-A-A-T-A-T-C-C-A-C-C-T-G-C-A-G-A-T-T-C-T-A-C-C-A-A-A-A-G-T-G-T-A-T-T-T-G- 146 bases

T-A-G-T-T-A-T-A-G-G-T-G-G-A-C-G-T-C-T-A-A-G-A-T-G-G-T-T-T-T-C-A-C-A-T-A-A-A-C- 146 bases

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.?

Chem Biol 17:1334-1343 (2010)

PubMed id: 21168769

Consequences of cisplatin binding on nucleosome structure and dynamics.

R.C.Todd, S.J.Lippard.

ABSTRACT

The effects of cisplatin binding to DNA were explored at the nucleosome level to incorporate key features of the eukaryotic nuclear environment. An X-ray crystal structure of a site-specifically platinated nucleosome carrying a 1,3-cis-{Pt(NH₃)₂}²+-d(GpTpG) intrastrand cross-link reveals the details of how this adduct dictates the rotational positioning of DNA in the nucleosome. Results from in vitro nucleosome mobility assays indicate that a single platinum adduct interferes with ATP-independent sliding of DNA around the octamer core. Data from in vitro transcription experiments suggest that RNA polymerases can successfully navigate along cisplatin-damaged DNA templates that contain nucleosomes, but stall when the transcription elongation complex physically contacts a platinum cross-link located on the template strand. These results provide information about the effects of cisplatin binding to nuclear DNA and enhance our understanding of the mechanism of transcription inhibition by platinum anticancer compounds.