9ZD6
Bacterial interstrand DNA crosslink glycosylase AlkX/YcaQ bound to DNA
Summary for 9ZD6
| Entry DOI | 10.2210/pdb9zd6/pdb |
| Descriptor | Cytoplasmic protein, DNA (5'-D(*TP*GP*AP*GP*TP*CP*GP*T*(3DR)P*GP*AP*TP*GP*AP*CP*CP*AP*C)-3'), DNA (5'-D(*GP*TP*GP*GP*TP*CP*AP*TP*CP*CP*AP*CP*GP*AP*CP*TP*CP*A)-3'), ... (6 entities in total) |
| Functional Keywords | dna glycosylase, interstrand dna crosslink, hydrolase, hydrolase-dna complex, hydrolase/dna |
| Biological source | Thermobifida fusca More |
| Total number of polymer chains | 4 |
| Total formula weight | 102401.62 |
| Authors | |
| Primary citation | Cai 蔡毓娟, Y.,Kunkle, D.E.,Edinbugh, M.D.,Skaar, E.P.,Eichman, B.F. DNA binding and lesion recognition by the bacterial interstrand DNA crosslink glycosylase AlkX. Biorxiv, 2025 Cited by PubMed Abstract: Interstrand DNA crosslinks (ICLs) are a highly toxic form of DNA damage. ICL repair in both eukaryotes and bacteria involves unhooking of the two strands by specialized DNA glycosylases. We recently established that the human pathogen contains an ICL glycosylase (AlkX) that facilitates pathogenesis and protects the bacteria from DNA damage and acid stress. However, the physical basis for glycosylase-catalyzed ICL unhooking is unknown. Here, we describe a crystal structure of AlkX bound to DNA representing a product of the ICL unhooking reaction. Mutational analysis of ICL unhooking and sensitivity to the crosslinking agent mechlorethamine enabled identification of several AlkX motifs critical for ICL repair. We also found that a genetic variant from an antibiotic-resistant strain of the human pathogen significantly reduced AlkX activity and increased sensitivity to DNA crosslinking. This work provides a structural basis for how bacterial ICL glycosylases recognize and repair DNA adducts and contributes additional evidence that ICL repair is important for fitness of human pathogens. PubMed: 41427321DOI: 10.64898/2025.12.11.693820 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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