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bioRxiv · 10.1101/2024.05.14.591795

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

Takeshita, K.·Sakai, N.·Ueno, G.·Horie, M.·Tsujino, H.·Arisawa, M.·Yamamoto, M.·Arai, M.·Yamashita, T.
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Abstract

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.

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Takeshita, K., Sakai, N., Ueno, G., Horie, M., Tsujino, H., Arisawa, M., Yamamoto, M., Arai, M., Yamashita, T.. 2024-05-14. A large pocket structure surrounding the catalytic center in the BCG protein from Mycobacterium tuberculosis. https://doi.org/10.1101/2024.05.14.591795

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