1MWJ

Crystal Structure of a MUG-DNA pseudo substrate complex

Summary for 1MWJ

• Entry DOI: 10.2210/pdb1mwj/pdb
• Related: 1MUG
• Descriptor: 5'-D(*CP*GP*CP*GP*A*GP*(DU)P*TP*CP*GP*CP*G)-3', G/U mismatch-specific DNA glycosylase (3 entities in total)
• Functional Keywords: rossmann fold, non-hydrolysable dna-complex, uracil recognition., hydrolase-dna complex, hydrolase/dna
• Biological source: Escherichia coli
• Cellular location: Cytoplasm : P0A9H1
• Total number of polymer chains: 2
• Total formula weight: 22361.72

Authors

Barrett, T.E.,Scharer, O.,Savva, R.,Brown, T.,Jiricny, J.,Verdine, G.L.,Pearl, L.H. (deposition date: 2002-09-30, release date: 2002-10-11, Last modification date: 2024-04-03)

Primary citation

Barrett, T.E.,Scharer, O.,Savva, R.,Brown, T.,Jiricny, J.,Verdine, G.L.,Pearl, L.H.
Crystal Structure of a thwarted mismatch glycosylase DNA repair complex
Embo J., 18:6599-6609, 1999

PubMed Abstract: The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. Despite low sequence homology, the MUG/TDG enzymes are structurally related to the uracil-DNA glycosylase enzymes, but have a very different mechanism for substrate recognition. We have now determined the crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non-hydrolysable deoxyuridine analogue mismatched with guanine, providing the first structure of an intact substrate-nucleotide productively bound to a hydrolytic DNA glycosylase. The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3, N(4)-ethenocytosine. Together with structures for the free enzyme and for an abasic-DNA product complex, the MUG-substrate analogue complex reveals the conformational changes accompanying the catalytic cycle of substrate binding, base excision and product release.

PubMed: 10581234
DOI: 10.1093/emboj/18.23.6599

Experimental method

X-RAY DIFFRACTION (2.85 Å)