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      Computational Exploration of Putative LuxR Solos in Archaea and Their Functional Implications in Quorum Sensing

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          Abstract

          LuxR solos are unexplored in Archaea, despite their vital role in the bacterial regulatory network. They assist bacteria in perceiving acyl homoserine lactones (AHLs) and/or non-AHLs signaling molecules for establishing intraspecies, interspecies, and interkingdom communication. In this study, we explored the potential LuxR solos of Archaea from InterPro v62.0 meta-database employing taxonomic, probable function, distribution, and evolutionary aspects to decipher their role in quorum sensing (QS). Our bioinformatics analyses showed that putative LuxR solos of Archaea shared few conserved domains with bacterial LuxR despite having less similarity within proteins. Functional characterization revealed their ability to bind various AHLs and/or non-AHLs signaling molecules that involve in QS cascades alike bacteria. Further, the phylogenetic study indicates that Archaeal LuxR solos (with less substitution per site) evolved divergently from bacteria and share distant homology along with instances of horizontal gene transfer. Moreover, Archaea possessing putative LuxR solos, exhibit the correlation between taxonomy and ecological niche despite being the inhabitant of diverse habitats like halophilic, thermophilic, barophilic, methanogenic, and chemolithotrophic. Therefore, this study would shed light in deciphering the role of the putative LuxR solos of Archaea to adapt varied habitats via multilevel communication with other organisms using QS.

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            Bacterial quorum sensing: its role in virulence and possibilities for its control.

            Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.
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              Protein-ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment.

              Identification of protein-ligand binding sites is critical to protein function annotation and drug discovery. However, there is no method that could generate optimal binding site prediction for different protein types. Combination of complementary predictions is probably the most reliable solution to the problem. We develop two new methods, one based on binding-specific substructure comparison (TM-SITE) and another on sequence profile alignment (S-SITE), for complementary binding site predictions. The methods are tested on a set of 500 non-redundant proteins harboring 814 natural, drug-like and metal ion molecules. Starting from low-resolution protein structure predictions, the methods successfully recognize >51% of binding residues with average Matthews correlation coefficient (MCC) significantly higher (with P-value <10(-9) in student t-test) than other state-of-the-art methods, including COFACTOR, FINDSITE and ConCavity. When combining TM-SITE and S-SITE with other structure-based programs, a consensus approach (COACH) can increase MCC by 15% over the best individual predictions. COACH was examined in the recent community-wide COMEO experiment and consistently ranked as the best method in last 22 individual datasets with the Area Under the Curve score 22.5% higher than the second best method. These data demonstrate a new robust approach to protein-ligand binding site recognition, which is ready for genome-wide structure-based function annotations. http://zhanglab.ccmb.med.umich.edu/COACH/
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                03 May 2017
                2017
                : 8
                : 798
                Affiliations
                [1]Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research Chandigarh, India
                Author notes

                Edited by: Frank T. Robb, University of Maryland, Baltimore, USA

                Reviewed by: Ralf Heermann, Ludwig-Maximilians-Universität München, Germany; Rodolfo García-Contreras, National Autonomous University of Mexico, Mexico; Christopher John Grim, United States Food and Drug Administration, USA

                *Correspondence: Manoj Kumar, manojk@ 123456imtech.res.in

                This article was submitted to Evolutionary and Genomic Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2017.00798
                5413776
                28515720
                1309e52b-59e1-4cc4-8098-0405b32db348
                Copyright © 2017 Rajput and Kumar.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 January 2017
                : 19 April 2017
                Page count
                Figures: 7, Tables: 2, Equations: 3, References: 90, Pages: 16, Words: 0
                Funding
                Funded by: Department of Biotechnology, Ministry of Science and Technology 10.13039/501100001407
                Award ID: GAP0001
                Funded by: Council of Scientific and Industrial Research 10.13039/501100001412
                Award ID: BSC0121
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                archaea,quorum-sensing,luxr solos,ligand-binding,phylogeny,ecological niche,extremophiles,bioinformatics analyses

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