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Ueno, G.

Publications and source records attributed to Ueno, G..

2 recordsLinked to original sources
bioRxiv2024

A large pocket structure surrounding the catalytic center in the BCG protein from Mycobacterium tuberculosis

The widespread prevalence of tuberculosis and the need for extensive chemotherapy in its treatment are caused by the ability of tuberculosis (TB) bacteria to enter a dormant state. Therefore, it is crucial to develop effective compounds that can inhibit the growth of TB bacteria in both the active and dormant states. Previous research has identified agelasine D (marine sponge-derived diterpene alkaloid) capable of resisting dormant mycobacteria. Additionally, BCG3185c has been designated as a target mycobacterial protein. In this study, the crystal structure of BCG3185c was determined at a resolution of 1.86 [A]. Analysis of this crystal structure revealed a large pocket toward the catalytic center of BCG3185c, which is potentially adequate for agelasine D binding. Based on the results of the interaction analysis between agelasine D and Bacillus Calmette-Guerin (BCG) proteins, it was inferred that the binding of agelasine D to this large pocket is crucial for suppressing the growth of Mycobacterium tuberculosis.

biochemistry↗
bioRxiv2020

On-rate modulation of cadherin interactions by chemical fragments

Many cadherin family proteins are associated with diseases such as cancer. Since cell adhesion requires homodimerization of cadherin molecules, a small-molecule regulator of dimerization would have therapeutic potential. Herein, we describe identification of a P-cadherin-specific chemical fragment that inhibits P-cadherin-mediated cell adhesion. Although the identified molecule is a fragment compound, it binds to a cavity of P-cadherin that has not previously been targeted, indirectly prevents formation of hydrogen bonds necessary for formation of an intermediate called the X dimer and thus modulates the on-rate of X dimerization. Our findings will impact on a strategy for kinetic regulation of protein-protein interactions and stepwise assembly of protein complexes using small molecules.

biochemistry↗