Structural dynamics of the N‐terminal <scp>SH2</scp> domain of <scp>PI3K</scp> in its free and <scp>CD28</scp>‐bound states

Hosoe, Yuhi; Miyanoiri, Yohei; Re, Suyong; Ochi, Saki; Asahina, Yuya; Kawakami, Toru; Kuroda, Masataka; Mizuguchi, Kenji; Oda, Masayuki

doi:10.1111/febs.16666

Cited by 3 publications

(4 citation statements)

References 51 publications

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Section: Resultsmentioning

confidence: 99%

“…Hosoe et al reported high RMSF values for the almost-similar loop region in the N-terminal SH2 domain of PI3K, which is a subunit of p85 showing ~25% sequence similarity with Drk-SH2 [ 26 ]. The reported MD data also indicated the formation of hydrogen bonds between the side-chain of S361, located in the loop region, with the pY present in the peptide derived from CD28 (SDpYMNMTPRRPG) [ 26 ]. Taken together with our results for Drk-SH2 and the results presented in these previously reported studies, the high RMSF commonly observed in this loop region may be directly related to the pY recognition mechanism; e.g., the capability to undergo additional structural changes to accommodate the pY residue.…”

Section: Resultsmentioning

confidence: 99%

“…Taken together with our results for Drk-SH2 and the results presented in these previously reported studies, the high RMSF commonly observed in this loop region may be directly related to the pY recognition mechanism; e.g., the capability to undergo additional structural changes to accommodate the pY residue. Hosoe et al reported high RMSF values for the almost-similar loop region in the Nterminal SH2 domain of PI3K, which is a subunit of p85 showing ~25% sequence similarity with Drk-SH2 [26]. The reported MD data also indicated the formation of hydrogen bonds between the side-chain of S361, located in the loop region, with the pY present in the peptide derived from CD28 (SDpYMNMTPRRPG) [26].…”

Section: Backbone Dynamics Of Drk-sh2mentioning

confidence: 95%

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Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase

Sayeesh,

Iguchi,

Inomata

et al. 2024

IJMS

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The Drosophila downstream receptor kinase (Drk), a homologue of human GRB2, participates in the signal transduction from the extracellular to the intracellular environment. Drk receives signals through the interaction of its Src homology 2 (SH2) domain with the phosphorylated tyrosine residue in the receptor tyrosine kinases (RTKs). Here, we present the solution NMR structure of the SH2 domain of Drk (Drk-SH2), which was determined in the presence of a phosphotyrosine (pY)-containing peptide derived from a receptor tyrosine kinase, Sevenless (Sev). The solution structure of Drk-SH2 possess a common SH2 domain architecture, consisting of three β strands imposed between two α helices. Additionally, we interpret the site-specific interactions of the Drk-SH2 domain with the pY-containing peptide through NMR titration experiments. The dynamics of Drk-SH2 were also analysed through NMR-relaxation experiments as well as the molecular dynamic simulation. The docking simulations of the pY-containing peptide onto the protein surface of Drk-SH2 provided the orientation of the peptide, which showed a good agreement with the analysis of the SH2 domain of GRB2.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Backbone Dynamics Of Drk-sh2mentioning

confidence: 95%

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Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase

Sayeesh,

Iguchi,

Inomata

et al. 2024

IJMS

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“…This is evident in original research contributions n this Focus Issue; for example, structural dynamics are highlighted in the work of Yuhi Hosoe et al . [14] in their analysis of the N‐terminal src homology 2 (SH2) domain of phosphoinositide 3‐kinase (PI3K) in bound and unbound states. Using crystallographic and biochemical assays, Ippei Watanabe and colleagues evaluate in detail the consequences of 4,6‐ O ‐disulfated disaccharide moieties in chondroitin sulfate E on the activity of chondrointinase ABC1 activity [15].…”

Section: Unravelling Complex Relationshipsmentioning

confidence: 99%

Unravelling the complexity of enzyme catalysis

Scrutton

2023

The FEBS Journal

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The study of enzymes never disappoints. Despite its long history-almost 150 years following the first documented use of the word enzyme in 1878the field of enzymology advances apace. This long journey has witnessed landmark developments that have defined modern enzymology as a broad discipline, leading to improved understanding at the molecular level, as we aspire to discover the complex relationships between enzyme structures, catalytic mechanisms and biological function. How enzymes are regulated at the gene and post-translational levels and how catalytic activity is modulated by interactions with small ligands and macromolecules, or the broader enzyme environment, are topical areas of study. Insights from such studies guide the exploitation of natural and engineered enzymes in biomedical or industrial processes; for example, in diagnostics, pharmaceuticals manufacture and processing technologies that use immobilised enzymes and enzyme reactor-based systems. In this Focus Issue, The FEBS Journal seeks to highlight breaking science and informative reviews, as well as personal reflections, to illustrate the breadth and importance of contemporary molecular enzymology research.

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Enhancing solution structural analysis of large molecular proteins through optimal stereo array isotope labeling of aromatic amino acids

Miyanoiri,

Takeda,

Okuma

et al. 2024

Biophysical Chemistry

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Structural dynamics of the N‐terminal SH2 domain of PI3K in its free and CD28‐bound states

Abstract: PYMOL [20]. (F) Snapshot of the hydrogen bond network stabilising the minor conformation.

Cited by 3 publications

References 51 publications

Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase

Structure and Dynamics of Drk-SH2 Domain and Its Site-Specific Interaction with Sev Receptor Tyrosine Kinase

Unravelling the complexity of enzyme catalysis

Enhancing solution structural analysis of large molecular proteins through optimal stereo array isotope labeling of aromatic amino acids

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