9CUN

Crystal structure of Ami1 from M. tuberculosis in complex with a tetrazole compound

これはPDB形式変換不可エントリーです。

9CUN の概要

• エントリーDOI: 10.2210/pdb9cun/pdb
• 分子名称: N-acetylmuramoyl-L-alanine amidase Rv3717, 5-(2-iodophenyl)-2H-tetrazole, ZINC ION, ... (4 entities in total)
• 機能のキーワード: amidase, peptidoglycan hydrolase, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23033.77

構造登録者

Martinez-Caballero, S. (登録日: 2024-07-26, 公開日: 2024-11-20, 最終更新日: 2024-12-11)

主引用文献

Rosas-Cruz, M.,Madariaga Mazon, A.,Garcia-Mejia, C.D.,Hernandez-Vazquez, E.,Gomez-Velasco, H.,Jimenez-Faraco, E.,Farias-Gaytan, R.S.,Hermoso, J.A.,Martinez-Caballero, S.
Identification of Potential Inhibitors of Mycobacterium tuberculosis Amidases: An Integrated In Silico and Experimental Study.
Acs Omega, 9:46461-46471, 2024

PubMed Abstract: Virtual screening is a crucial tool in early stage drug discovery for identifying potential hit candidates. Here, we present an integrated approach that combines theoretical and experimental techniques to identify, for the first time, inhibitors of amidases (Ami1-Ami4) from . Through computational methods, we proposed a set of potential inhibitors, which were subsequently evaluated experimentally using differential scanning fluorimetry. This led to the identification of two promising hits: a carbohydrazide core (hit ) and a tetrazole core (hit ). We further developed a small collection of compounds derived from hit , which demonstrated improved affinity for Ami1. Additionally, we determined the crystallographic structure of the Ami1-hit complex at a resolution of 1.45 Å, providing molecular-level insights into the interaction of this compound within the catalytic site. The findings of this study contribute to the advancement of drug discovery against tuberculosis and propose new targets for therapeutic development.

PubMed: 39583660
DOI: 10.1021/acsomega.4c07964

実験手法

X-RAY DIFFRACTION (1.45 Å)