1SSP

WILD-TYPE URACIL-DNA GLYCOSYLASE BOUND TO URACIL-CONTAINING DNA

Summary for 1SSP

• Entry DOI: 10.2210/pdb1ssp/pdb
• Descriptor: 5'-D(*CP*TP*GP*TP*(D1P)P*AP*TP*CP*TP*T)-3', 5'-D(*AP*AP*AP*GP*AP*TP*AP*AP*CP*AP*G)-3', URACIL-DNA GLYCOSYLASE, ... (5 entities in total)
• Functional Keywords: dna glycosylase, dna base excision repair, uracil, dna, protein/dna, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Mitochondrion. Isoform 2: Nucleus: P13051
• Total number of polymer chains: 3
• Total formula weight: 31948.38

Authors

Parikh, S.S.,Mol, C.D.,Slupphaug, G.,Bharati, S.,Krokan, H.E.,Tainer, J.A. (deposition date: 1999-04-28, release date: 1999-05-06, Last modification date: 2023-08-02)

Primary citation

Parikh, S.S.,Mol, C.D.,Slupphaug, G.,Bharati, S.,Krokan, H.E.,Tainer, J.A.
Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA.
EMBO J., 17:5214-5226, 1998

PubMed Abstract: Three high-resolution crystal structures of DNA complexes with wild-type and mutant human uracil-DNA glycosylase (UDG), coupled kinetic characterizations and comparisons with the refined unbound UDG structure help resolve fundamental issues in the initiation of DNA base excision repair (BER): damage detection, nucleotide flipping versus extrahelical nucleotide capture, avoidance of apurinic/apyrimidinic (AP) site toxicity and coupling of damage-specific and damage-general BER steps. Structural and kinetic results suggest that UDG binds, kinks and compresses the DNA backbone with a 'Ser-Pro pinch' and scans the minor groove for damage. Concerted shifts in UDG simultaneously form the catalytically competent active site and induce further compression and kinking of the double-stranded DNA backbone only at uracil and AP sites, where these nucleotides can flip at the phosphate-sugar junction into a complementary specificity pocket. Unexpectedly, UDG binds to AP sites more tightly and more rapidly than to uracil-containing DNA, and thus may protect cells sterically from AP site toxicity. Furthermore, AP-endonuclease, which catalyzes the first damage-general step of BER, enhances UDG activity, most likely by inducing UDG release via shared minor groove contacts and flipped AP site binding. Thus, AP site binding may couple damage-specific and damage-general steps of BER without requiring direct protein-protein interactions.

PubMed: 9724657
DOI: 10.1093/emboj/17.17.5214

Experimental method

X-RAY DIFFRACTION (1.9 Å)