5SV2

Toxin VapC21 from Mycobacterium tuberculosis

5SV2 の概要

• エントリーDOI: 10.2210/pdb5sv2/pdb
• 分子名称: Ribonuclease VapC21 (2 entities in total)
• 機能のキーワード: toxin-antitoxin, vapc, vapbc, rnase, vapc21, hydrolase
• 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: 16825.16

構造登録者

Valadares, N.F. (登録日: 2016-08-04, 公開日: 2016-09-14, 最終更新日: 2023-10-04)

主引用文献

Jardim, P.,Santos, I.C.,Barbosa, J.A.R.G.,de Freitas, S.M.,Valadares, N.F.
Crystal structure of VapC21 from Mycobacterium tuberculosis at 1.31 angstrom resolution.
Biochem.Biophys.Res.Commun., 478:1370-1375, 2016

PubMed Abstract: Persisters are individual bacterial cells that exhibit a phenotype characterized by slow growth, low metabolic rate and multidrug tolerance. The processes that drive cells into a persistence state constitute an active but incipient research field, and structural data regarding its components are scarce. The molecular targets of many therapeutic drugs are involved in cell wall synthesis and cell division, and these cellular processes are down-regulated in persister cells, consequently these cells are more likely to survive antibiotic treatment. Toxin-antitoxin systems were shown to have a leading role in the formation of persisters, and several pathogenic bacteria display a wide array of these systems. The Mycobacterium tuberculosis H37Rv genome presents 88 toxin-antitoxin loci, of which 47 code for members of the VapBC protein family. To date, only four crystal structures of Mycobacterium tuberculosis VapBC complexes are available, and all of them present the toxin bound to and inhibited by the antitoxin. We present the 1.31 Å resolution structure of VapC21, the first structure of a Mycobacterium tuberculosis VapC toxin in the absence of its cognate inhibitory antitoxin. Our data show that VapC21 is a dimer in solution, with conserved active site architecture and an extensive antitoxin binding groove. Additionally, the strategy used to mutate a putative catalytic residue allowing the expression and purification of soluble VapC21 will pave the way for the resolution of more toxin structures in the absence of antitoxins. Taken together, our findings represent an important step in unraveling the molecular mechanisms related to persistence, which will contribute for the design of faster and more efficient therapeutic approaches for the treatment of tuberculosis, particularly for infections with multidrug-resistant strains.

PubMed: 27576202
DOI: 10.1016/j.bbrc.2016.08.130

実験手法

X-RAY DIFFRACTION (1.31 Å)