PDBsum entry 6plc

DNA binding protein/DNA

PDB id: 6plc

Contents

Protein chain

430 a.a.

DNA/RNA

Ligands

XG4

GOL

Metals

_MG ×2

Waters ×51

PDB id:

6plc

Name:

DNA binding protein/DNA

Title:

Structure of human DNA polymerase eta complexed with 8oa in the template base paired with incoming non-hydrolyzable gtp

Structure:

DNA polymerase eta. Chain: a. Synonym: rad30 homolog a,xeroderma pigmentosum variant type protein. Engineered: yes. DNA (5'-d( Cp Ap Tp (A38)p Ap Tp Gp Ap Cp Gp Cp T)-3'). Chain: t. Engineered: yes. DNA (5'-d( Ap Gp Cp Gp Tp Cp Ap T)-3'). Chain: p.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: polh, rad30, rad30a, xpv. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.50Å R-factor: 0.183 R-free: 0.273

Authors:

M.C.Koag,S.Lee

Key ref:

M.C.Koag et al. (2020). Mutagenesis mechanism of the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine. Nucleic Acids Res, 48, 5119-5134. PubMed id: 32282906 DOI: 10.1093/nar/gkaa193

Date:

30-Jun-19 Release date: 22-Apr-20

Protein chain

Q9Y253  (POLH_HUMAN) -  DNA polymerase eta from Homo sapiens

Seq: 713 a.a.

Struc: 430 a.a.

DNA/RNA chains

C-A-T-A38-A-T-G-A-C-G-C-T 12 bases

A-G-C-G-T-C-A-T 8 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: 10.1093/nar/gkaa193

Nucleic Acids Res 48:5119-5134 (2020)

PubMed id: 32282906

Mutagenesis mechanism of the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine.

M.C.Koag, H.Jung, S.Lee.

ABSTRACT

Reactive oxygen species generate the genotoxic 8-oxoguanine (oxoG) and 8-oxoadenine (oxoA) as major oxidative lesions. The mutagenicity of oxoG is attributed to the lesion's ability to evade the geometric discrimination of DNA polymerases by adopting Hoogsteen base pairing with adenine in a Watson-Crick-like geometry. Compared with oxoG, the mutagenesis mechanism of oxoA, which preferentially induces A-to-C mutations, is poorly understood. In the absence of protein contacts, oxoA:G forms a wobble conformation, the formation of which is suppressed in the catalytic site of most DNA polymerases. Interestingly, human DNA polymerase η (polη) proficiently incorporates dGTP opposite oxoA, suggesting the nascent oxoA:dGTP overcomes the geometric discrimination of polη. To gain insights into oxoA-mediated mutagenesis, we determined crystal structures of polη bypassing oxoA. When paired with dGTP, oxoA adopted a syn-conformation and formed Hoogsteen pairing while in a wobble geometry, which was stabilized by Gln38-mediated minor groove contacts to oxoA:dGTP. Gln38Ala mutation reduced misinsertion efficiency ∼55-fold, indicating oxoA:dGTP misincorporation was promoted by minor groove interactions. Also, the efficiency of oxoA:dGTP insertion by the X-family polβ decreased ∼380-fold when Asn279-mediated minor groove contact to dGTP was abolished. Overall, these results suggest that, unlike oxoG, oxoA-mediated mutagenesis is greatly induced by minor groove interactions.