Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states.

التفاصيل البيبلوغرافية
العنوان:	Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states.
المؤلفون:	Takahashi, Diane T., Gadelle, Danièle, Agama, Keli, Kiselev, Evgeny, Zhang, Hongliang, Yab, Emilie, Petrella, Stephanie, Forterre, Patrick, Pommier, Yves, Mayer, Claudine
المصدر:	Nature Communications; 1/10/2022, Vol. 13 Issue 1, p1-11, 11p
مصطلحات موضوعية:	DNA topoisomerase I, DEOXYRIBOZYMES, ENZYME kinetics, CAMPTOTHECIN, DNA, CRYSTAL structure
مستخلص:	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. Topoisomerase I (TOP1) relaxes both positive and negative supercoils by nicking DNA and after rotation of the broken DNA strand closes the nick. Here, the authors present the DNA free crystal structure of TOP1 from the hyperthermophilic archaeon Caldiarchaeum subterraneum in the open form and discuss the mechanism of how DNA enters the catalytic site of TOP1. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات:	Complementary Index

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