PDBsum entry 5mcu

Transcription

PDB id: 5mcu

Contents

Protein chains

197 a.a.

DNA/RNA

Ligands

EDO ×6

Metals

_ZN ×2

Waters ×432

PDB id:

5mcu

Name:

Transcription

Title:

New insights into the role of DNA shape on its recognition by p53 proteins (complex p53dbd-lhg2)

Structure:

Cellular tumor antigen p53. Chain: a, b. Fragment: p53 DNA binding domain. Synonym: antigen ny-co-13,phosphoprotein p53,tumor suppressor p53. Engineered: yes. DNA. Chain: c. Fragment: DNA. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tp53, p53. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Resolution:

1.70Å R-factor: 0.170 R-free: 0.201

Authors:

D.Golovenko,H.Rozenberg,Z.Shakked

Key ref:

D.Golovenko et al. (2018). New Insights into the Role of DNA Shape on Its Recognition by p53 Proteins. Structure, 26, 1237. PubMed id: 30057026 DOI: 10.1016/j.str.2018.06.006

Date:

10-Nov-16 Release date: 13-Jun-18

Protein chains

P04637  (P53_HUMAN) -  Cellular tumor antigen p53 from Homo sapiens

Seq: 393 a.a.

Struc: 197 a.a.

DNA/RNA chain

G-G-G-C-IGU-T-G-C-C-C-G-G-G-C-IGU-T-G-C-C-C 20 bases

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.str.2018.06.006

Structure 26:1237 (2018)

PubMed id: 30057026

New Insights into the Role of DNA Shape on Its Recognition by p53 Proteins.

D.Golovenko, B.Bräuning, P.Vyas, T.E.Haran, H.Rozenberg, Z.Shakked.

ABSTRACT

The tumor suppressor p53 acts as a transcription factor recognizing diverse DNA response elements (REs). Previous structural studies of p53-DNA complexes revealed non-canonical Hoogsteen geometry of A/T base pairs at conserved CATG motifs leading to changes in DNA shape and its interface with p53. To study the effects of DNA shape on binding characteristics, we designed REs with modified base pairs "locked" into either Hoogsteen or Watson-Crick form. Here we present crystal structures of these complexes and their thermodynamic and kinetic parameters, demonstrating that complexes with Hoogsteen base pairs are stabilized relative to those with all-Watson-Crick base pairs. CATG motifs are abundant in p53REs such as GADD45 and p53R2 related to cell-cycle arrest and DNA repair. The high-resolution structures of these complexes validate their propensity to adopt the unique Hoogsteen-induced structure, thus providing insights into the functional role of DNA shape and broadening the mechanisms that contribute to DNA recognition by proteins.