9CUN

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

This is a non-PDB format compatible entry.

Summary for 9CUN

• Entry DOI: 10.2210/pdb9cun/pdb
• Descriptor: N-acetylmuramoyl-L-alanine amidase Rv3717, 5-(2-iodophenyl)-2H-tetrazole, ZINC ION, ... (4 entities in total)
• Functional Keywords: amidase, peptidoglycan hydrolase, hydrolase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 23033.77

Authors

Martinez-Caballero, S. (deposition date: 2024-07-26, release date: 2024-11-20, Last modification date: 2024-12-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.45 Å)