3UBY

Crystal structure of human alklyadenine DNA glycosylase in a lower and higher-affinity complex with DNA

Summary for 3UBY

• Entry DOI: 10.2210/pdb3uby/pdb
• Related: 1BNK 1EWN 1F4R 1F6O 3QI5
• Descriptor: DNA-3-methyladenine glycosylase, DNA (5'-D(*GP*AP*CP*AP*TP*GP*(EDC)P*TP*TP*GP*CP*CP*T)-3') (3 entities in total)
• Functional Keywords: alkyladenine dna glycosylase fold, aag, dna repair, dna binding, nucleus, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Potential): P29372
• Total number of polymer chains: 4
• Total formula weight: 56562.97

Authors

Setser, J.W.,Lingaraju, G.M.,Davis, C.A.,Samson, L.D.,Drennan, C.L. (deposition date: 2011-10-25, release date: 2011-12-28, Last modification date: 2023-09-13)

Primary citation

Setser, J.W.,Lingaraju, G.M.,Davis, C.A.,Samson, L.D.,Drennan, C.L.
Searching for DNA lesions: structural evidence for lower- and higher-affinity DNA binding conformations of human alkyladenine DNA glycosylase.
Biochemistry, 51:382-390, 2012

PubMed Abstract: To efficiently repair DNA, human alkyladenine DNA glycosylase (AAG) must search the million-fold excess of unmodified DNA bases to find a handful of DNA lesions. Such a search can be facilitated by the ability of glycosylases, like AAG, to interact with DNA using two affinities: a lower-affinity interaction in a searching process and a higher-affinity interaction for catalytic repair. Here, we present crystal structures of AAG trapped in two DNA-bound states. The lower-affinity depiction allows us to investigate, for the first time, the conformation of this protein in the absence of a tightly bound DNA adduct. We find that active site residues of AAG involved in binding lesion bases are in a disordered state. Furthermore, two loops that contribute significantly to the positive electrostatic surface of AAG are disordered. Additionally, a higher-affinity state of AAG captured here provides a fortuitous snapshot of how this enzyme interacts with a DNA adduct that resembles a one-base loop.

PubMed: 22148158
DOI: 10.1021/bi201484k

Experimental method

X-RAY DIFFRACTION (2 Å)