Computational elucidation of the binding mechanisms of curcumin analogues as bacterial RecA inhibitors

Abstract

A mechanistic insights into bacterial RecA protein as a target for curcumin-like compounds offers a theoretical basis for rational design and development of future antibiotic adjuvants.

Pharmacophore screening, denovo designing, retrosynthetic analysis, and combinatorial synthesis of a novel lead VTRA1.1 against RecA protein of Acinetobacter baumannii

“…coli and M . tuberculosis (Zhou et al, 2019 ) that suggest designing of hybrid molecules may have emerged as a promising way to target RecA protein. There has been no hybrid inhibitor or denovo designed lead against RecA of A .…”

“…coli and M . tuberculosis (Zhou et al, 2019) suggesting hybrid molecules may be promising to target RecA protein. Most of the reported inhibitors are designed against RecA of E .…”

“…There are different studies reported inhibitors targeting bacterial RecA protein such as suramin for Mycobacterium tuberculosis (Nautiyal et al, 2014), and naphthalene polysulfonated compounds (Zhou et al, 2021), N6-(1-naphthyl)-ADP (Lee et al, 2005), designed helix (Cline et al, 2007), Phthalocyanine tetrasulfonic acid (Alam et al, 2016), alpha-helical peptide of RecX protein against the RecA of Escherichia coli (Yakimov et al, 2017). Recently, curcumin-thalidomide hybrids show high predicted binding to RecA compared to the curcumin analogs in E. coli and M. tuberculosis (Zhou et al, 2019) suggesting hybrid molecules may be promising to target RecA protein. Most of the reported inhibitors are designed against RecA of E. coli and M. tuberculosis, but there is no inhibitor/drug available targeting RecA protein of A. baumannii except in silico screening lead ZINC01530654 .…”

Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds

“…Similarly, in addition to the ATPase activity center (pocket A), binding events at neighboring pockets such as pocket B and pocket D could modulate RecA protein conformation, with yet unclarified physiological functions. In our previous study (Zhou et al, 2019), structural attributes of the residues in pocket B were analyzed by multiple algorithms. However, none of such residues in pocket B have so far been reported to play significant roles in RecA-related protein-protein interactions.…”

“…(Leis et al, 2010). Recently, our group successfully applied these approaches to map out RecA protein-binding determinants and predict binders among curcuminoid compounds (Zhou et al, 2019). In this present study, the phylogenetically relevant features within the RecA protein sequence, probabilistically favorable pocketness in the RecA protein structure, and predicted mechanisms underlying interactions between RecA and NPS of interest were scrutinized.…”