8CZQ

The crystal structure of MtbTOP1 in complex with both G- and T-segments

Summary for 8CZQ

• Entry DOI: 10.2210/pdb8czq/pdb
• Descriptor: DNA topoisomerase 1, DNA (5'-D(*CP*TP*TP*CP*CP*GP*CP*TP*TP*GP*AP*C)-3'), GLYCEROL, ... (5 entities in total)
• Functional Keywords: topoisomerase 1, mycobacterium tuberculosis, g-segment, t-segment, isomerase, isomerase-dna complex, isomerase/dna
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 4
• Total formula weight: 89699.56

Authors

Tan, K.,Tse-Dinh, Y.-C. (deposition date: 2022-05-25, release date: 2022-12-14, Last modification date: 2023-10-25)

Primary citation

Ferdous, S.,Dasgupta, T.,Annamalai, T.,Tan, K.,Tse-Dinh, Y.C.
The interaction between transport-segment DNA and topoisomerase IA-crystal structure of MtbTOP1 in complex with both G- and T-segments.
Nucleic Acids Res., 51:349-364, 2023

PubMed Abstract: Each catalytic cycle of type IA topoisomerases has been proposed to comprise multistep reactions. The capture of the transport-segment DNA (T-segment) into the central cavity of the N-terminal toroidal structure is an important action, which is preceded by transient gate-segment (G-segment) cleavage and succeeded by G-segment religation for the relaxation of negatively supercoiled DNA and decatenation of DNA. The T-segment passage in and out of the central cavity requires significant domain-domain rearrangements, including the movement of D3 relative to D1 and D4 for the opening and closing of the gate towards the central cavity. Here we report a direct observation of the interaction of a duplex DNA in the central cavity of a type IA topoisomerase and its associated domain-domain conformational changes in a crystal structure of a Mycobacterium tuberculosis topoisomerase I complex that also has a bound G-segment. The duplex DNA within the central cavity illustrates the non-sequence-specific interplay between the T-segment DNA and the enzyme. The rich structural information revealed from the novel topoisomerase-DNA complex, in combination with targeted mutagenesis studies, provides new insights into the mechanism of the topoisomerase IA catalytic cycle.

PubMed: 36583363
DOI: 10.1093/nar/gkac1205

Experimental method

X-RAY DIFFRACTION (2.78 Å)