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

Abstract

AbstractThe 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 Å. 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 andBacillusCalmette-Guérin (BCG) proteins, it was inferred that the binding of agelasine D to this large pocket is crucial for suppressing the growth ofMycobacterium tuberculosis.