5VI0

Pseudomonas fluorescens alkylpurine DNA glycosylase AlkC bound to DNA containing an abasic site analog

Summary for 5VI0

• Entry DOI: 10.2210/pdb5vi0/pdb
• Related: 5VHV
• Descriptor: alkylpurine DNA glycosylase AlkC, DNA (5'-D(*TP*GP*TP*CP*CP*AP*(3DR)P*GP*TP*CP*T)-3'), DNA (5'-D(*AP*AP*GP*AP*CP*TP*TP*GP*GP*AP*C)-3'), ... (6 entities in total)
• Functional Keywords: dna alkylation repair enzyme, hydrolase-dna complex, hydrolase/dna
• Biological source: Pseudomonas fluorescens; More
• Total number of polymer chains: 6
• Total formula weight: 97303.22

Authors

Shi, R.,Eichman, B.F. (deposition date: 2017-04-13, release date: 2017-10-25, Last modification date: 2024-11-20)

Primary citation

Shi, R.,Mullins, E.A.,Shen, X.X.,Lay, K.T.,Yuen, P.K.,David, S.S.,Rokas, A.,Eichman, B.F.
Selective base excision repair of DNA damage by the non-base-flipping DNA glycosylase AlkC.
EMBO J., 37:63-74, 2018

PubMed Abstract: DNA glycosylases preserve genome integrity and define the specificity of the base excision repair pathway for discreet, detrimental modifications, and thus, the mechanisms by which glycosylases locate DNA damage are of particular interest. Bacterial AlkC and AlkD are specific for cationic alkylated nucleobases and have a distinctive HEAT-like repeat (HLR) fold. AlkD uses a unique non-base-flipping mechanism that enables excision of bulky lesions more commonly associated with nucleotide excision repair. In contrast, AlkC has a much narrower specificity for small lesions, principally N3-methyladenine (3mA). Here, we describe how AlkC selects for and excises 3mA using a non-base-flipping strategy distinct from that of AlkD. A crystal structure resembling a catalytic intermediate complex shows how AlkC uses unique HLR and immunoglobulin-like domains to induce a sharp kink in the DNA, exposing the damaged nucleobase to active site residues that project into the DNA This active site can accommodate and excise N3-methylcytosine (3mC) and N1-methyladenine (1mA), which are also repaired by AlkB-catalyzed oxidative demethylation, providing a potential alternative mechanism for repair of these lesions in bacteria.

PubMed: 29054852
DOI: 10.15252/embj.201797833

Experimental method

X-RAY DIFFRACTION (2.396 Å)