6Z03

DNA Topoisomerase

Summary for 6Z03

• Entry DOI: 10.2210/pdb6z03/pdb
• Descriptor: DNA topoisomerase I (2 entities in total)
• Functional Keywords: topoisomerase, dna binding protein
• Biological source: Caldiarchaeum subterraneum
• Total number of polymer chains: 2
• Total formula weight: 127166.51

Authors

Takahashi, T.S.,Gadelle, D.,Forterre, P.,Mayer, C.,Petrella, S. (deposition date: 2020-05-07, release date: 2021-11-17, Last modification date: 2024-02-07)

Primary citation

Takahashi, D.T.,Gadelle, D.,Agama, K.,Kiselev, E.,Zhang, H.,Yab, E.,Petrella, S.,Forterre, P.,Pommier, Y.,Mayer, C.
Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states.
Nat Commun, 13:59-59, 2022

PubMed Abstract: Eukaryotic topoisomerases I (TOP1) are ubiquitous enzymes removing DNA torsional stress. However, there is little data concerning the three-dimensional structure of TOP1 in the absence of DNA, nor how the DNA molecule can enter/exit its closed conformation. Here, we solved the structure of thermostable archaeal Caldiarchaeum subterraneum CsTOP1 in an apo-form. The enzyme displays an open conformation resulting from one substantial rotation between the capping (CAP) and the catalytic (CAT) modules. The junction between these two modules is a five-residue loop, the hinge, whose flexibility permits the opening/closing of the enzyme and the entry of DNA. We identified a highly conserved tyrosine near the hinge as mediating the transition from the open to closed conformation upon DNA binding. Directed mutagenesis confirmed the importance of the hinge flexibility, and linked the enzyme dynamics with sensitivity to camptothecin, a TOP1 inhibitor targeting the TOP1 enzyme catalytic site in the closed conformation.

PubMed: 35013228
DOI: 10.1038/s41467-021-27686-7

Experimental method

X-RAY DIFFRACTION (2.2 Å)