PDBsum entry 3d1f

Transferase, transcription

PDB id: 3d1f

Contents

Protein chains

366 a.a. *

Ligands

SER-GLU-GLN-VAL-GLU-LEU-GLU-PHE-ASP ×2

PEG ×2

323 ×2

Waters ×558

* Residue conservation analysis

PDB id:

3d1f

Name:

Transferase, transcription

Title:

Crystal structure of e. Coli sliding clamp (beta) bound to a polymerase iii peptide

Structure:

DNA polymerase iii subunit beta. Chain: a, b. Engineered: yes. Nonapeptide from polymerase iii c-terminal. Chain: p, q. Engineered: yes. Other_details: n-terminal of the peptide is labeled with a rhodamine 6g (dye)

Source:

Escherichia coli. Strain: k12. Gene: dnan. Expressed in: escherichia coli. Synthetic: yes. Other_details: the sequence occurs naturally in e. Coli

Resolution:

2.00Å R-factor: 0.217 R-free: 0.255

Authors:

R.E.Georgescu,O.Yurieva,K.Seung-Sup,J.Kuriyan,X.-P.Kong,M.O'Donnell

Key ref:

R.E.Georgescu et al. (2008). Structure of a small-molecule inhibitor of a DNA polymerase sliding clamp. Proc Natl Acad Sci U S A, 105, 11116-11121. PubMed id: 18678908 DOI: 10.1073/pnas.0804754105

Date:

05-May-08 Release date: 29-Jul-08

Protein chains

P0A988  (DPO3B_ECOLI) -  Beta sliding clamp from Escherichia coli (strain K12)

Seq: 366 a.a.

Struc: 366 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1073/pnas.0804754105

Proc Natl Acad Sci U S A 105:11116-11121 (2008)

PubMed id: 18678908

Structure of a small-molecule inhibitor of a DNA polymerase sliding clamp.

R.E.Georgescu, O.Yurieva, S.S.Kim, J.Kuriyan, X.P.Kong, M.O'Donnell.

ABSTRACT

DNA polymerases attach to the DNA sliding clamp through a common overlapping binding site. We identify a small-molecule compound that binds the protein-binding site in the Escherichia coli beta-clamp and differentially affects the activity of DNA polymerases II, III, and IV. To understand the molecular basis of this discrimination, the cocrystal structure of the chemical inhibitor is solved in complex with beta and is compared with the structures of Pol II, Pol III, and Pol IV peptides bound to beta. The analysis reveals that the small molecule localizes in a region of the clamp to which the DNA polymerases attach in different ways. The results suggest that the small molecule may be useful in the future to probe polymerase function with beta, and that the beta-clamp may represent an antibiotic target.

Selected figure(s)

Figure 3.
Structure of a small-molecule inhibitor bound to the β-clamp. (A) The RU7 compound. (B) Distances between RU7 and the β-clamp. Side-chain movements upon binding RU7 are indicated. Yellow and white are residues of β in the absence or presence of RU7, respectively. Distances between RU7 and protein residues are marked in black; the distances 3.73, 3.41, and 3.03 Å are marked a, b, and c, respectively.

Figure 5.
Superposition of Pol II, III, and IV peptides and RU7 compound bound to β. (A) Superposition of the Pol III peptide (green), Pol II peptide (blue), and Pol IV peptide (purple; PDB ID code 1OK7) (10). (B) Superposition of Pol III peptide (green) and the RU7 compound (orange). The surface of the β-clamp is colored white, and the protein-binding pocket of β is colored according to sequence conservation of an alignment of 42 bacterial subunits; the color scale proceeds from red (90% conservation) to yellow (50% conservation). Circled regions in the peptide-binding pocket indicate subsites 1 and 2. Figures were prepared by using Pymol (27).

Figures were selected by an automated process.