2XZF

CRYSTAL STRUCTURE OF A COMPLEX BETWEEN THE WILD-TYPE LACTOCOCCUS LACTIS FPG (MUTM) AND AN OXIDIZED PYRIMIDINE CONTAINING DNA AT 293K

Summary for 2XZF

• Entry DOI: 10.2210/pdb2xzf/pdb
• Related: 1KFV 1NNJ 1PJI 1PJJ 1PM5 1TDZ 1XC8
• Descriptor: FORMAMIDOPYRIMIDINE-DNA GLYCOSYLASE, 5'-D(*CP*TP*CP*TP*TP*TP*VETP*TP*TP*TP*CP*TP*CP*GP)-3', 5'-D(*GP*AP*GP*AP*AP*AP*CP*AP*AP*AP*GP*AP*GP*CP)-3', ... (6 entities in total)
• Functional Keywords: hydrolase-dna complex, hydrolase/dna
• Biological source: LACTOCOCCUS LACTIS SUBSP. CREMORIS; More
• Total number of polymer chains: 3
• Total formula weight: 39810.33

Authors

LeBihan, Y.V.,Izquierdo, M.A.,Coste, F.,Culard, F.,Gehrke, T.H.,Essalhi, K.,Aller, P.,Carrel, T.,Castaing, B. (deposition date: 2010-11-25, release date: 2011-10-05, Last modification date: 2023-12-20)

Primary citation

Le Bihan, Y.V.,Izquierdo, M.A.,Coste, F.,Aller, P.,Culard, F.,Gehrke, T.H.,Essalhi, K.,Carrel, T.,Castaing, B.
5-Hydroxy-5-Methylhydantoin DNA Lesion, a Molecular Trap for DNA Glycosylases
Nucleic Acids Res., 39:6277-, 2011

PubMed Abstract: DNA base-damage recognition in the base excision repair (BER) is a process operating on a wide variety of alkylated, oxidized and degraded bases. DNA glycosylases are the key enzymes which initiate the BER pathway by recognizing and excising the base damages guiding the damaged DNA through repair synthesis. We report here biochemical and structural evidence for the irreversible entrapment of DNA glycosylases by 5-hydroxy-5-methylhydantoin, an oxidized thymine lesion. The first crystal structure of a suicide complex between DNA glycosylase and unrepaired DNA has been solved. In this structure, the formamidopyrimidine-(Fapy) DNA glycosylase from Lactococcus lactis (LlFpg/LlMutM) is covalently bound to the hydantoin carbanucleoside-containing DNA. Coupling a structural approach by solving also the crystal structure of the non-covalent complex with site directed mutagenesis, this atypical suicide reaction mechanism was elucidated. It results from the nucleophilic attack of the catalytic N-terminal proline of LlFpg on the C5-carbon of the base moiety of the hydantoin lesion. The biological significance of this finding is discussed.

PubMed: 21486746
DOI: 10.1093/NAR/GKR215

Experimental method

X-RAY DIFFRACTION (1.799 Å)