1ssp

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spinqualitylabelsall models 1ssp, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Immunodeficiency with hyper IgM, type 4 OMIM:[191525]

About this Structure

1SSP is a Single protein structure of sequence from Homo sapiens with URA as ligand. Active as Uridine nucleosidase, with EC number 3.2.2.3 Full crystallographic information is available from OCA.

Reference

Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA., Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA, EMBO J. 1998 Sep 1;17(17):5214-26. PMID:9724657

Page seeded by OCA on Mon Nov 12 19:17:24 2007