3GO8

MutM encountering an intrahelical 8-oxoguanine (oxoG) lesion in EC3-loop deletion complex

Summary for 3GO8

• Entry DOI: 10.2210/pdb3go8/pdb
• Related: 3GPP 3GPU 3GPX 3GQ3 3GQ4 3GQ5 3GQY
• Descriptor: Formamidopyrimidine-DNA glycosylase, 5'-D(P*GP*GP*TP*AP*GP*AP*TP*CP*CP*GP*GP*AP*CP*G)-3', 5'-D(*GP*CP*GP*TP*CP*CP*(8OG)P*GP*AP*TP*CP*TP*AP*C)-3', ... (5 entities in total)
• Functional Keywords: dna glycosylase, dna repair, damage search, base extrusion, disulfide crosslinking, dna damage, dna-binding, glycosidase, hydrolase, lyase, metal-binding, multifunctional enzyme, zinc-finger, lyase-dna complex, lyase/dna
• Biological source: Geobacillus stearothermophilus (Bacillus stearothermophilus); More
• Total number of polymer chains: 3
• Total formula weight: 38735.26

Authors

Spong, M.C.,Qi, Y.,Verdine, G.L. (deposition date: 2009-03-18, release date: 2009-12-15, Last modification date: 2023-09-06)

Primary citation

Qi, Y.,Spong, M.C.,Nam, K.,Banerjee, A.,Jiralerspong, S.,Karplus, M.,Verdine, G.L.
Encounter and extrusion of an intrahelical lesion by a DNA repair enzyme
Nature, 462:762-766, 2009

PubMed Abstract: How living systems detect the presence of genotoxic damage embedded in a million-fold excess of undamaged DNA is an unresolved question in biology. Here we have captured and structurally elucidated a base-excision DNA repair enzyme, MutM, at the stage of initial encounter with a damaged nucleobase, 8-oxoguanine (oxoG), nested within a DNA duplex. Three structures of intrahelical oxoG-encounter complexes are compared with sequence-matched structures containing a normal G base in place of an oxoG lesion. Although the protein-DNA interfaces in the matched complexes differ by only two atoms-those that distinguish oxoG from G-their pronounced structural differences indicate that MutM can detect a lesion in DNA even at the earliest stages of encounter. All-atom computer simulations show the pathway by which encounter of the enzyme with the lesion causes extrusion from the DNA duplex, and they elucidate the critical free energy difference between oxoG and G along the extrusion pathway.

PubMed: 20010681
DOI: 10.1038/nature08561

Experimental method

X-RAY DIFFRACTION (1.89 Å)