PDBsum entry 4m2y

Transferase/DNA

PDB id: 4m2y

Contents

Protein chain

319 a.a.

DNA/RNA

Metals

_NA ×2

Waters ×72

PDB id:

4m2y

Name:

Transferase/DNA

Title:

Structure of human DNA polymerase beta complexed with 8-brg as the template base in a 1-nucleotide gapped DNA

Structure:

DNA polymerase beta. Chain: a. Engineered: yes. Template DNA strand. Chain: t. Engineered: yes. Up-primer. Chain: p. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: polb. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this is a synthetic sequence.. Other_details: this is complementary sequence upstream of gap..

Resolution:

2.27Å R-factor: 0.215 R-free: 0.269

Authors:

M.C.Koag,K.Min,A.F.Monzingo,S.Lee

Key ref:

M.C.Koag et al. (2014). Structural basis for promutagenicity of 8-halogenated guanine. J Biol Chem, 289, 6289-6298. PubMed id: 24425881 DOI: 10.1074/jbc.M113.537803

Date:

05-Aug-13 Release date: 22-Jan-14

Protein chain

P06746  (DPOLB_HUMAN) -  DNA polymerase beta from Homo sapiens

Seq: 335 a.a.

Struc: 319 a.a.

DNA/RNA chains

C-C-G-A-C-BGM-T-C-G-C-A-T-C-A-G-C 16 bases

G-C-T-G-A-T-G-C-G-A 10 bases

G-T-C-G-G 5 bases

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 2: E.C.4.2.99.- - ?????
• Enzyme class 3: E.C.4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase.
• Reaction: 2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)- 2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho- 2'-deoxyribonucleoside-DNA + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

Added reference

DOI no: 10.1074/jbc.M113.537803

J Biol Chem 289:6289-6298 (2014)

PubMed id: 24425881

Structural basis for promutagenicity of 8-halogenated guanine.

M.C.Koag, K.Min, S.Lee.

ABSTRACT

8-Halogenated guanine (haloG), a major DNA adduct formed by reactive halogen species during inflammation, is a promutagenic lesion that promotes misincorporation of G opposite the lesion by various DNA polymerases. Currently, the structural basis for such misincorporation is unknown. To gain insights into the mechanism of misincorporation across haloG by polymerase, we determined seven x-ray structures of human DNA polymerase β (polβ) bound to DNA bearing 8-bromoguanine (BrG). We determined two pre-catalytic ternary complex structures of polβ with an incoming nonhydrolyzable dGTP or dCTP analog paired with templating BrG. We also determined five binary complex structures of polβ in complex with DNA containing BrG·C/T at post-insertion and post-extension sites. In the BrG·dGTP ternary structure, BrG adopts syn conformation and forms Hoogsteen base pairing with the incoming dGTP analog. In the BrG·dCTP ternary structure, BrG adopts anti conformation and forms Watson-Crick base pairing with the incoming dCTP analog. In addition, our polβ binary post-extension structures show Hoogsteen BrG·G base pair and Watson-Crick BrG·C base pair. Taken together, the first structures of haloG-containing DNA bound to a protein indicate that both BrG·G and BrG·C base pairs are accommodated in the active site of polβ. Our structures suggest that Hoogsteen-type base pairing between G and C8-modified G could be accommodated in the active site of a DNA polymerase, promoting G to C mutation.