PDBsum entry 2dpi

Transferase/DNA

PDB id: 2dpi

Contents

Protein chain

372 a.a. *

DNA/RNA

Ligands

DCP

Metals

_MG ×2

Waters ×122

* Residue conservation analysis

PDB id:

2dpi

Name:

Transferase/DNA

Title:

Ternary complex of hpoli with DNA and dctp

Structure:

5'-d( Ap Gp Gp Ap Cp Cp (Doc))-3'. Chain: p. Engineered: yes. 5'-d( Tp (Eda)p Gp Gp Gp Tp Cp Cp T)-3'. Chain: t. Engineered: yes. DNA polymerase iota. Chain: a. Fragment: residues 1-420.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: rad30 homolog b, eta2. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.

Biol. unit:

Hexamer (from PDB file)

Resolution:

2.30Å R-factor: 0.232 R-free: 0.278

Authors:

D.T.Nair,R.E.Johnson,L.Prakash,S.Prakash,A.K.Aggarwal

Key ref:

D.T.Nair et al. (2006). Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota. Nat Struct Mol Biol, 13, 619-625. PubMed id: 16819516 DOI: 10.1038/nsmb1118

Date:

12-May-06 Release date: 04-Jul-06

Protein chain

Q9UNA4  (POLI_HUMAN) -  DNA polymerase iota from Homo sapiens

Seq: 740 a.a.

Struc: 372 a.a.

DNA/RNA chains

A-G-G-A-C-C-DOC 7 bases

T-EDA-G-G-G-T-C-C-T 9 bases

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: 10.1038/nsmb1118

Nat Struct Mol Biol 13:619-625 (2006)

PubMed id: 16819516

Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota.

D.T.Nair, R.E.Johnson, L.Prakash, S.Prakash, A.K.Aggarwal.

ABSTRACT

The 1,N6-ethenodeoxyadenosine (epsilon dA) lesion is promutagenic and has been implicated in carcinogenesis. We show here that human Pol iota, a Y-family DNA polymerase, can promote replication through this lesion by proficiently incorporating a nucleotide opposite it. The structural basis of this action is rotation of the epsilon dA adduct to the syn conformation in the Pol iota active site and presentation of its 'Hoogsteen edge' for hydrogen-bonding with incoming dTTP or dCTP. We also show that Pol zeta carries out the subsequent extension reaction and that efficiency of extension from epsilon dA x T is notably higher than from epsilon dA x C. Together, our studies reveal for the first time how the exocyclic epsilon dA adduct is accommodated in a DNA polymerase active site, and they show that the combined action of Pol iota and Pol zeta provides for efficient and error-free synthesis through this potentially carcinogenic DNA lesion.

Selected figure(s)

Figure 1.
Figure 1. Hoogsteen pairing of dA with T or C. (a) Chemical structures of A and dA. (b) Hoogsteen base pair of syn-A in syn with anti-T or anti-C. Jagged line represents steric clash between the N6 group of A and the N4 of C. (c) Hoogsteen base pair of dA with T or C. Dotted lines represent hydrogen bonds and R denotes the sugar moiety.

Figure 5.
Figure 5. Primer extension by Pol and Pol from T or C opposite the dA adduct. DNA substrate is shown above; asterisk indicates the site of either an A or an dA residue in the template; Y at the primer terminus denotes either T or C opposite the undamaged A or the dA template residue. Each protein (1 nM) was incubated with DNA substrate (10 nM) and all four dNTPs (50 M).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 619-625) copyright 2006.

Figures were selected by an automated process.