Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

Lee, Byung-Gil; Kim, Min Kyung; Song, Hyun Kyu

doi:10.1007/s10059-011-0197-1

Cited by 50 publications

(76 citation statements)

References 47 publications

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“…These two rings are interconnected by E helices, resulting in a cylindrical shape with a height of 86 Å. The helix is similar to previously reported structures in the active and extended form (10,12,17,18); the complex height, however, resembles the inactive and bent form (11,13,15,34). The residues forming the catalytic triad (Ser98, His123, and Asp172) of LmClpP2 are misaligned in all 14 subunits (Fig.…”

Section: Resultssupporting

confidence: 84%

Structural and functional insights into caseinolytic proteases reveal an unprecedented regulation principle of their catalytic triad

Zeiler

List

Alte

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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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.

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Section: Resultssupporting

confidence: 84%

Structural and functional insights into caseinolytic proteases reveal an unprecedented regulation principle of their catalytic triad

Zeiler

List

Alte

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…Furthermore, the hetero-oligomeric ClpP of Listeria monocytogenes displays activity only in tetradecameric assemblies as recently published (37). Hence, mutations of Glu 135 and Leu 144 abolish activity due to a defect in oligomerization and not, as stated recently, due to a defect of product release (25).…”

supporting

confidence: 51%

“…Fourth, in the case of B. subtilis, crystals of the compressed and of the extended form have been found next to each other in the same crystallization well (25). This unambiguously points to the fact that both conformations exist in solution.…”

mentioning

confidence: 59%

“…Although a similar conformation was observed before in the structures of Mycobacterium tuberculosis, P. falciparum, Streptococcus pneumonia (A153P), the full handle domain in this compressed state could be observed for the first time in the SaClpP structure. This region shows no defined electron density in the other structures including a recent structure of the B. subtilis ClpP in the compressed state (25). Looking through the ClpP entries in the Protein Data Bank, one notes that all ClpP structures fall into two categories: either they show an extended E helix and a catalytic triad in its active rearrangement, or they show a compressed cylinder ϳ1 nm smaller in height with unaligned active site residues (for a complete list, see supplemental Table 2).…”

mentioning

confidence: 89%

“…Structures of ClpP in the compressed state comprise that of M. tuberculosis (pH 8.0), P. falciparum (pH 7.0), and B. subtilis (pH 5.6) (see supplemental Table 2). All of these structures show the characteristic compressed form of the cylinder (18,20,25).…”

mentioning

confidence: 99%

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Insights into Structural Network Responsible for Oligomerization and Activity of Bacterial Virulence Regulator Caseinolytic Protease P (ClpP) Protein

Gersch

List

Groll

et al. 2012

Journal of Biological Chemistry

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The Nϵ‐Rule for Serine, but Not Cysteine Catalytic Triads

Czapinska

Bochtler

2022

Angewandte Chemie

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Catalytic triads, composed of a serine or cysteine nucleophile, a histidine, and a third triad residue (typically Asp/Glu/Asn), are common in enzyme active sites and catalyze a wide variety of chemical reactions. Two types of triads can be distinguished: We refer to them as Nδ-or Nɛ-configured, depending on whether the histidine imidazole Nδ or Nɛ atom is close to the nucleophile Oγ/Sγ. In this study, we have analyzed triad configuration. In structural triads, the more stable Nδ-configuration predominates. For catalytic triads, the configuration depends on the nucleophile. When it is a cysteine residue, both configuration types occur, depending on the family. However, when the nucleophile is a serine residue, the less stable Nɛ-configuration is almost exclusively found. We posit that the energetically less favored conformation is selected for in serine triads to facilitate the otherwise difficult proton transfer from the nucleophile to the histidine residue.

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Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

Cited by 50 publications

References 47 publications

Structural and functional insights into caseinolytic proteases reveal an unprecedented regulation principle of their catalytic triad

Structural and functional insights into caseinolytic proteases reveal an unprecedented regulation principle of their catalytic triad

Insights into Structural Network Responsible for Oligomerization and Activity of Bacterial Virulence Regulator Caseinolytic Protease P (ClpP) Protein

The Nϵ‐Rule for Serine, but Not Cysteine Catalytic Triads

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