Yutaka Kofuku

Pre-miR-21 Conformational Equilibrium Modulates the Efficacy of the Maturation Inhibitor L50

Yuhei Nishimura, Yuji Tokunaga, Yutaka Kofuku, Yutaro Shiraishi et autres

The cyclic peptide L50 is a promising anticancer candidate that inhibits miR-21 maturation by targeting the Dicer cleavage site of pre-miR-21. A recent study revealed that pre-miR-21 exists in equilibrium between an Ade-29-deprotonated Bulged state and a Dicer-susceptible Ade-29-protonated Paired state. However, …

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Cell Permeability and Target Engagement of Middle-Sized Molecules Quantified by In-Cell NMR

Yota Sukigara, Hajime Kamoshida, Yuji Tokunaga, Miwa Fujisaki et autres

Middle-sized molecules, such as macrocycles and cyclic peptides, are gaining attention as novel drug modalities due to their ability to permeate into cells and interfere with intracellular protein-protein interactions (PPIs). However, predicting and measuring the cell permeability of middle-sized molecules remains challenging, …

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Author response for "Structural basis of the residence time of adenosine A2A receptor ligands revealed by NMR"

Takumi Ueda, Tomoki Tsuchida, Masanori Kurita, Takuya Mizumura et autres

Two-step target recognition for the competitive inhibition activity of an anti-VEGF aptamer.

Koh Takeuchi, Takumi Ueda, Misaki Imai, Miwa Fujisaki et autres

The anti-vascular endothelial growth factor (VEGF) aptamer, t44.27, is a 27-mer RNA that functions as the active component of pegaptanib, an anti-angiogenic medicine for neovascular age-related macular degeneration. The t44.27 aptamer is extensively 2′-modified and tightly binds to the heparin-binding domain (HDB) …

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Author response for "Structural basis of the residence time of adenosine A2A receptor ligands revealed by NMR"

Takumi Ueda, Tomoki Tsuchida, Masanori Kurita, Takuya Mizumura et autres

Structure and Function-Associated Dynamics of Membrane Proteins Unveiled by Solution NMR

Koh Takeuchi, Yutaka Kofuku, Shunsuke Imai, Yuji Tokunaga et autres

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Structural basis of the residence time of adenosine A 2A receptor ligands revealed by NMR

Takumi Ueda, Tomoki Tsuchida, Takuya Mizumura, Shunsuke Imai et autres

AR under conditions where E165Q and T256A mutations led to reduced residence times. Our NMR analysis revealed that the spatial arrangement surrounding the E165-H264 salt bridge correlates with residence time. These findings provide quantitative insights into residence time and could assist in …

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Affinity-directed substrate/H+-antiport by a MATE transporter

Koh Takeuchi, Takumi Ueda, Misaki Imai, Miwa Fujisaki et autres

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Function-Related Conformational Dynamics of GPCRs Revealed by Solution NMR

Takumi Ueda, Yutaka Kofuku, Koh Takeuchi, Shunsuke Imai et autres

NMR methods provide information about conformational dynamics of GPCRs over a wide range of frequencies in aqueous media at near-physiological temperature, with minimal modification of the wild-type GPCR covalent structures. Here we review our solution NMR studies of the functionrelated conformational dynamics …

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Activation mechanism of the μ-opioid receptor by an allosteric modulator

Shun Kaneko, Shunsuke Imai, Nobuaki Asao, Yutaka Kofuku et autres

Allosteric modulators of G-protein-coupled receptors (GPCRs) enhance signaling by binding to GPCRs concurrently with their orthosteric ligands, offering a novel approach to overcome the efficacy limitations of conventional orthosteric ligands. However, the structural mechanism by which allosteric modulators mediate GPCR signaling remains …

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Biphasic activation of β-arrestin 1 upon interaction with a GPCR revealed by methyl-TROSY NMR

Yutaro Shiraishi, Yutaka Kofuku, Takumi Ueda, Shubhi Pandey et autres

β-arrestins (βarrs) play multifaceted roles in the function of G protein-coupled receptors (GPCRs). βarrs typically interact with phosphorylated C-terminal tail (C tail) and transmembrane core (TM core) of GPCRs. However, the effects of the C tail- and TM core-mediated interactions on the …

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GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures

Ichio Shimada, Takumi Ueda, Yutaka Kofuku, Matthew T. Eddy et autres

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