5D5H

Crystal structure of Mycobacterium tuberculosis Topoisomerase I

5D5H の概要

• エントリーDOI: 10.2210/pdb5d5h/pdb
• 分子名称: DNA topoisomerase 1, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: topoisomerase, isomerase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 78567.05

構造登録者

Tan, K.,Cheng, B.,Tse-Dinh, Y.C. (登録日: 2015-08-10, 公開日: 2015-12-16, 最終更新日: 2024-03-06)

主引用文献

Tan, K.,Cao, N.,Cheng, B.,Joachimiak, A.,Tse-Dinh, Y.C.
Insights from the Structure of Mycobacterium tuberculosis Topoisomerase I with a Novel Protein Fold.
J.Mol.Biol., 428:182-193, 2016

PubMed Abstract: The DNA topoisomerase I enzyme of Mycobacterium tuberculosis (MtTOP1) is essential for the viability of the organism and survival in a murine model. This topoisomerase is being pursued as a novel target for the discovery of new therapeutic agents for the treatment of drug-resistant tuberculosis. In this study, we succeeded in obtaining a structure of MtTOP1 by first predicting that the C-terminal region of MtTOP1 contains four repeated domains that do not involve the Zn-binding tetracysteine motifs seen in the C-terminal domains of Escherichia coli topoisomerase I. A construct (amino acids A2-T704), MtTOP1-704t, that includes the N-terminal domains (D1-D4) and the first predicted C-terminal domain (D5) of MtTOP1 was expressed and found to retain DNA cleavage-religation activity and catalyze single-stranded DNA catenation. MtTOP1-704t was crystallized, and a structure of 2.52Å resolution limit was obtained. The structure of the MtTOP1 N-terminal domains has features that have not been observed in other previously available bacterial topoisomerase I crystal structures. The first C-terminal domain D5 forms a novel protein fold of a four-stranded antiparallel β-sheet stabilized by a crossing-over α-helix. Since there is only one type IA topoisomerase present in Mycobacteriaceae and related Actinobacteria, this subfamily of type IA topoisomerase may be required for multiple functions in DNA replication, transcription, recombination, and repair. The unique structural features observed for MtTOP1 may allow these topoisomerase I enzymes to carry out physiological functions associated with topoisomerase III enzyme in other bacteria.

PubMed: 26655023
DOI: 10.1016/j.jmb.2015.11.024

実験手法

X-RAY DIFFRACTION (2.52 Å)