6TTY

Structure of ClpP from Staphylococcus aureus (apo, closed state)

6TTY の概要

• エントリーDOI: 10.2210/pdb6tty/pdb
• 関連するPDBエントリー: 3V5E
• 分子名称: ATP-dependent Clp protease proteolytic subunit (2 entities in total)
• 機能のキーワード: caseinolytic protease, allosteric regulation, extended conformation, closed state, hydrolase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 316101.52

構造登録者

Malik, I.T.,Pereira, R.,Vielberg, M.-T.,Mayer, C.,Straetener, J.,Thomy, D.,Famulla, K.,Castro, H.C.,Sass, P.,Groll, M.,Broetz-Oesterheldt, H. (登録日: 2019-12-30, 公開日: 2020-03-25, 最終更新日: 2024-01-24)

主引用文献

Malik, I.T.,Pereira, R.,Vielberg, M.T.,Mayer, C.,Straetener, J.,Thomy, D.,Famulla, K.,Castro, H.,Sass, P.,Groll, M.,Brotz-Oesterhelt, H.
Functional Characterisation of ClpP Mutations Conferring Resistance to Acyldepsipeptide Antibiotics in Firmicutes.
Chembiochem, 21:1997-2012, 2020

PubMed Abstract: Acyldepsipeptide (ADEP) is an exploratory antibiotic with a novel mechanism of action. ClpP, the proteolytic core of the caseinolytic protease, is deregulated towards unrestrained proteolysis. Here, we report on the mechanism of ADEP resistance in Firmicutes. This bacterial phylum contains important pathogens that are relevant for potential ADEP therapy. For Staphylococcus aureus, Bacillus subtilis, enterococci and streptococci, spontaneous ADEP-resistant mutants were selected in vitro at a rate of 10 . All isolates carried mutations in clpP. All mutated S. aureus ClpP proteins characterised in this study were functionally impaired; this increased our understanding of the mode of operation of ClpP. For molecular insights, crystal structures of S. aureus ClpP bound to ADEP4 were determined. Well-resolved N-terminal domains in the apo structure allow the pore-gating mechanism to be followed. The compilation of mutations presented here indicates residues relevant for ClpP function and suggests that ADEP resistance will occur at a lower rate during the infection process.

PubMed: 32181548
DOI: 10.1002/cbic.201900787

実験手法

X-RAY DIFFRACTION (1.9 Å)