PDBsum entry 1rrs

Hydrolase/DNA

PDB id: 1rrs

Contents

Protein chain

345 a.a. *

DNA/RNA

Ligands

SF4

Metals

_CA

Waters ×95

* Residue conservation analysis

PDB id:

1rrs

Name:

Hydrolase/DNA

Title:

Muty adenine glycosylase in complex with DNA containing an abasic site

Structure:

5'-d( Ap Ap Gp Ap Cp (8Og)p Tp Gp Gp Ap C)-3'. Chain: b. Engineered: yes. 5'-d( Tp Gp Tp Cp Cp Ap (Hpd)p Gp Tp Cp T)-3'. Chain: c. Engineered: yes. Muty. Chain: a. Engineered: yes.

Source:

Synthetic: yes. Geobacillus stearothermophilus. Organism_taxid: 1422. Gene: muty. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Trimer (from PQS)

Resolution:

2.40Å R-factor: 0.231 R-free: 0.275

Authors:

J.C.Fromme,A.Banerjee,S.J.Huang,G.L.Verdine

Key ref:

J.C.Fromme et al. (2004). Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase. Nature, 427, 652-656. PubMed id: 14961129 DOI: 10.1038/nature02306

Date:

08-Dec-03 Release date: 17-Feb-04

Protein chain

P83847  (MUTY_GEOSE) -  Adenine DNA glycosylase from Geobacillus stearothermophilus

Seq: 366 a.a.

Struc: 345 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

A-A-G-A-C-8OG-T-G-G-A-C 11 bases

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

Enzyme reactions

• Enzyme class: E.C.3.2.2.31 - adenine glycosylase.

DOI no: 10.1038/nature02306

Nature 427:652-656 (2004)

PubMed id: 14961129

Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase.

J.C.Fromme, A.Banerjee, S.J.Huang, G.L.Verdine.

ABSTRACT

The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base.

Selected figure(s)

Figure 2.
Figure 2: MutY -DNA complex. a, Ribbon trace of the complex. DNA is shown in gold, oxoG in magenta, the substrate adenine in purple, the [4Fe -4S] domain in green, and the six-helix barrel domain in cyan. The C-terminal domain is coloured by secondary structure ( -strands, blue; helices, red). The sulphur and iron atoms of the [4Fe -4S] cluster are yellow and orange, respectively. See Supplementary Fig. S4 for a topology diagram. b, Same structure as in a, but rotated 90° towards the reader. The purple sphere indicates a Ca^2+ ion that is occluded in a. c, Structures of MutT13 and the EndoIII -DNA complex9. N and C termini are indicated.

Figure 3.
Figure 3: Enzyme -DNA interface and oxoG recognition. a, GRASP24 molecular surface representation of the enzyme, with the bound DNA shown as a framework model. Residues Gln 48, Tyr 88 and Ser 308 are indicated and the DNA is coloured as in Fig. 1. b, Ball-and-stick representation of the view shown in a. OxoG is shown in red, the substrate adenine in purple, and the remainder of the DNA in gold. The protein backbone is presented as a grey ribbon trace, with side chains shown explicitly in cyan. c, Close-up view of oxoG recognition by MutY (coloured as in a). Broken lines indicate inferred hydrogen bonds.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 427, 652-656) copyright 2004.

Figures were selected by an automated process.