Flavanones: A potential natural inhibitor of the ATP binding site of PknG of Mycobacterium tuberculosis.

Over the years, Mycobacterium tuberculosis has been one of the major causes of death worldwide. As several clinical isolates of the bacteria have developed drug resistance against the target sites of the current therapeutic agents, the development of a novel drug is the pressing priority. According to recent studies on Mycobacterium tuberculosis, ATP binding sites of Mycobacterium tuberculosis serine/threonine protein kinases (MTPKs) have been identified as the new promising drug target. Among the several other protein kinases (PKs), Protein kinase G (PknG) was selected for the study because of its crucial role in modulating bacterium's metabolism to survive in host macrophages. In this work, we have focused on the H37Rv strain of Mycobacterium tuberculosis. A list of 477 flavanones obtained from the PubChem database was docked one by one against the crystallized and refined structure of PknG by in-silico techniques. Initially, potential inhibitors were narrowed down by preliminary docking. Flavanones were then selected using binding energies ranging from -7.9 kcal.mol-1 to -10.8 kcal.mol-1. This was followed by drug-likeness prediction, redocking analysis, and molecular dynamics simulations. Here, we have used experimentally confirmed drug AX20017 as a reference to determine candidate compounds that can act as potential inhibitors for PknG. PubChem165506, PubChem242065, PubChem688859, PubChem101367767, PubChem3534982, and PubChem42607933 were identified as possible target site inhibitors for PknG with a desirable negative binding energy of -8.1, -8.3, -8.4, -8.8, -8.6 and -7.9 kcal.mol-1 respectively. Communicated by Ramaswamy H. Sarma.

In-silico genome wide analysis of Mitogen activated protein kinase kinase kinase gene family in C. sinensis.

Mitogen activated protein kinase kinase kinase (MAPKKK) form the upstream component of MAPK cascade. It is well characterized in several plants such as Arabidopsis and rice however the knowledge about MAPKKKs in tea plant is largely unknown. In the present study, MAPKKK genes of tea were obtained through a genome wide search using Arabidopsis thaliana as the reference genome. Among 59 candidate MAPKKK genes in tea, 17 genes were MEKK-like, 31 genes were Raf-like and 11 genes were ZIK- like. Additionally, phylogenetic relationships were established along with structural analysis, which includes gene structure, its location as well as conserved motifs, cis-acting regulatory elements and functional domain signatures that were systematically examined. Also, on the basis of one orthologous gene found between tea and Arabidopsis, functional interaction was carried out in C. sinensis based on an Arabidopsis association model. The expressional profiles indicated major involvement of MAPKKK genes from tea in response to various abiotic stress factors. Taken together, this study provides the targets for additional inclusive identification, functional study, and provides comprehensive knowledge for a better understanding of the MAPKKK cascade regulatory network in C. sinensis.

NHX Gene Family in Camellia sinensis: In-silico Genome-Wide Identification, Expression Profiles, and Regulatory Network Analysis.

Salt stress affects the plant growth and productivity worldwide and NHX is one of those genes that are well known to improve salt tolerance in transgenic plants. It is well characterized in several plants, such as Arabidopsis thaliana and cotton; however, not much is known about NHXs in tea plant. In the present study, NHX genes of tea were obtained through a genome-wide search using A. thaliana as reference genome. Out of the 9 NHX genes in tea, 7 genes were localized in vacuole while the remaining 2 genes were localized in the endoplasmic reticulum (ER; CsNHX8) and plasma membrane (PM; CsNHX9), respectively. Furthermore, phylogenetic relationships along with structural analysis which includes gene structure, location, and protein-conserved motifs and domains were systematically examined and further, predictions were validated by the expression analysis. The dN/dS values show that the majority of tea NHX genes is subjected to strong purifying selection under the course of evolution. Also, functional interaction was carried out in Camellia sinensis based on the orthologous genes in A. thaliana. The expression profiles linked to various stress treatments revealed wide involvement of NHX genes from tea in response to various abiotic factors. This study provides the targets for further comprehensive identification, functional study, and also contributed for a better understanding of the NHX regulatory network in C. sinensis.