4JCR

ClpP1 N165D mutant from Listeria monocytogenes

4JCR の概要

• エントリーDOI: 10.2210/pdb4jcr/pdb
• 関連するPDBエントリー: 1TYF 2FZS 3V5E 4JCQ
• 分子名称: ATP-dependent Clp protease proteolytic subunit (2 entities in total)
• 機能のキーワード: pathogenic bacteria, virulence factor, regulation, clp protease family, active catalytic triad, hydrolase
• 由来する生物種: Listeria monocytogenes
• 細胞内の位置: Cytoplasm (By similarity): Q8Y7Y1
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 317836.43

構造登録者

Zeiler, E.,List, A.,Alte, F.,Gersch, M.,Wachtel, R.,Groll, M.,Sieber, S. (登録日: 2013-02-22, 公開日: 2013-06-12, 最終更新日: 2023-09-20)

主引用文献

Zeiler, E.,List, A.,Alte, F.,Gersch, M.,Wachtel, R.,Poreba, M.,Drag, M.,Groll, M.,Sieber, S.A.
Structural and functional insights into caseinolytic proteases reveal an unprecedented regulation principle of their catalytic triad.
Proc.Natl.Acad.Sci.USA, 110:11302-11307, 2013

PubMed Abstract: Caseinolytic proteases (ClpPs) are large oligomeric protein complexes that contribute to cell homeostasis as well as virulence regulation in bacteria. Although most organisms possess a single ClpP protein, some organisms encode two or more ClpP isoforms. Here, we elucidated the crystal structures of ClpP1 and ClpP2 from pathogenic Listeria monocytogenes and observe an unprecedented regulation principle by the catalytic triad. Whereas L. monocytogenes (Lm)ClpP2 is both structurally and functionally similar to previously studied tetradecameric ClpP proteins from Escherichia coli and Staphylococcus aureus, heptameric LmClpP1 features an asparagine in its catalytic triad. Mutation of this asparagine to aspartate increased the reactivity of the active site and led to the assembly of a tetradecameric complex. We analyzed the heterooligomeric complex of LmClpP1 and LmClpP2 via coexpression and subsequent labeling studies with natural product-derived probes. Notably, the LmClpP1 peptidase activity is stimulated 75-fold in the complex providing insights into heterooligomerization as a regulatory mechanism. Collectively, our data point toward different preferences for substrates and inhibitors of the two ClpP enzymes and highlight their structural and functional characteristics.

PubMed: 23798410
DOI: 10.1073/pnas.1219125110

実験手法

X-RAY DIFFRACTION (2.1 Å)