6ZT3

N-terminal 47 kDa fragment of the Mycobacterium smegmatis DNA Gyrase B subunit complexed with ADPNP

6ZT3 の概要

• エントリーDOI: 10.2210/pdb6zt3/pdb
• 分子名称: DNA gyrase subunit B, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: type iia topoisomerase, atpase domain, ghkl superfamily, isomerase
• 由来する生物種: Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47966.48

構造登録者

Feng, L.,Mundy, J.E.A.,Stevenson, C.E.M.,Mitchenall, L.A.,Lawson, D.M.,Mi, K.,Maxwell, A. (登録日: 2020-07-17, 公開日: 2021-03-03, 最終更新日: 2024-01-31)

主引用文献

Feng, L.,Mundy, J.E.A.,Stevenson, C.E.M.,Mitchenall, L.A.,Lawson, D.M.,Mi, K.,Maxwell, A.
The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: DNA gyrase, a type II topoisomerase, introduces negative supercoils into DNA using ATP hydrolysis. The highly effective gyrase-targeted drugs, fluoroquinolones (FQs), interrupt gyrase by stabilizing a DNA-cleavage complex, a transient intermediate in the supercoiling cycle, leading to double-stranded DNA breaks. MfpA, a pentapeptide-repeat protein in mycobacteria, protects gyrase from FQs, but its molecular mechanism remains unknown. Here, we show that MfpA (MsMfpA) inhibits negative supercoiling by gyrase (Msgyrase) in the absence of FQs, while in their presence, MsMfpA decreases FQ-induced DNA cleavage, protecting the enzyme from these drugs. MsMfpA stimulates the ATPase activity of Msgyrase by directly interacting with the ATPase domain (MsGyrB47), which was confirmed through X-ray crystallography of the MsMfpA-MsGyrB47 complex, and mutational analysis, demonstrating that MsMfpA mimics a T (transported) DNA segment. These data reveal the molecular mechanism whereby MfpA modulates the activity of gyrase and may provide a general molecular basis for the action of other pentapeptide-repeat proteins.

PubMed: 33836580
DOI: 10.1073/pnas.2016705118

実験手法

X-RAY DIFFRACTION (1.56 Å)