7YKN

Crystal structure of (6-4) photolyase from Vibrio cholerae

Summary for 7YKN

• Entry DOI: 10.2210/pdb7ykn/pdb
• Descriptor: Cryptochrome/photolyase family protein, GLYCEROL, 1-deoxy-1-(6,7-dimethyl-2,4-dioxo-3,4-dihydropteridin-8(2H)-yl)-D-ribitol, ... (7 entities in total)
• Functional Keywords: photolyase, dna repair, dmrl, [4fe-4s] cluster, fad, lyase
• Biological source: Vibrio cholerae
• Total number of polymer chains: 1
• Total formula weight: 63385.80

Authors

Cakilkaya, B.,Kavakli, I.H.,DeMirci, H. (deposition date: 2022-07-23, release date: 2022-12-21, Last modification date: 2023-11-29)

Primary citation

Cakilkaya, B.,Kavakli, I.H.,DeMirci, H.
The crystal structure of Vibrio cholerae (6-4) photolyase reveals interactions with cofactors and a DNA-binding region.
J.Biol.Chem., 299:102794-102794, 2023

PubMed Abstract: Photolyases (PLs) reverse UV-induced DNA damage using blue light as an energy source. Of these PLs, (6-4) PLs repair (6-4)-lesioned photoproducts. We recently identified a gene from Vibrio cholerae (Vc) encoding a (6-4) PL, but structural characterization is needed to elucidate specific interactions with the chromophore cofactors. Here, we determined the crystal structure of Vc (6-4) PL at 2.5 Å resolution. Our high-resolution structure revealed that the two well-known cofactors, flavin adenine dinucleotide and the photoantenna 6,7-dimethyl 8-ribityl-lumazin (DMRL), stably interact with an α-helical and an α/β domain, respectively. Additionally, the structure has a third cofactor with distinct electron clouds corresponding to a [4Fe-4S] cluster. Moreover, we identified that Asp106 makes a hydrogen bond with water and DMRL, which indicates further stabilization of the photoantenna DMRL within Vc (6-4) PL. Further analysis of the Vc (6-4) PL structure revealed a possible region responsible for DNA binding. The region located between residues 478 to 484 may bind the lesioned DNA, with Arg483 potentially forming a salt bridge with DNA to stabilize further the interaction of Vc (6-4) PL with its substrate. Our comparative analysis revealed that the DNA lesion could not bind to the Vc (6-4) PL in a similar fashion to the Drosophila melanogaster (Dm, (6-4)) PL without a significant conformational change of the protein. The 23rd helix of the bacterial (6-4) PLs seems to have remarkable plasticity, and conformational changes facilitate DNA binding. In conclusion, our structure provides further insight into DNA repair by a (6-4) PL containing three cofactors.

PubMed: 36528063
DOI: 10.1016/j.jbc.2022.102794

Experimental method

X-RAY DIFFRACTION (2.5 Å)