Reduction in Structural Disorder and Functional Complexity in the Thermal Adaptation of Prokaryotes

Genomic correlates of evolutionary adaptation to very low or very high optimal growth temperature (OGT) values have been the subject of many studies. Whereas these provided a protein-structural rationale of the activity and stability of globular proteins/enzymes, the point has been neglected that adaptation to extreme temperatures could also have resulted from an increased use of intrinsically disordered proteins (IDPs), which are resistant to these conditions in vitro. Contrary to these expectations, we found a conspicuously low level of structural disorder in bacteria of very high (and very low) OGT values. This paucity of disorder does not reflect phylogenetic relatedness, i.e. it is a result of genuine adaptation to extreme conditions. Because intrinsic disorder correlates with important regulatory functions, we asked how these bacteria could exist without IDPs by studying transcription factors, known to harbor a lot of function-related intrinsic disorder. Hyperthermophiles have much less transcription factors, which have reduced disorder compared to their mesophilic counterparts. On the other hand, we found by systematic categorization of proteins with long disordered regions that there are certain functions, such as translation and ribosome biogenesis that depend on structural disorder even in hyperthermophiles. In all, our observations suggest that adaptation to extreme conditions is achieved by a significant functional simplification, apparent at both the level of the genome and individual genes/proteins

The structure of Jann_2411 (DUF1470) from Jannaschia sp. at 1.45 Å resolution reveals a new fold (the ABATE domain) and suggests its possible role as a transcription regulator

The crystal structure of the first representative of the Pfam PF07336 (DUF1470) family reveals a two-domain organization that contains a new fold, termed the ABATE domain, at the N-terminus and a treble-clef zinc finger that is likely to bind DNA at the C-terminus

The structure of the first representative of Pfam family PF09836 reveals a two-domain organization and suggests involvement in transcriptional regulation

The crystal structure of the NGO1945 gene product from N. gonorrhoeae (UniProt Q5F5IO) reveals that the N-terminal domain assigned as a domain of unknown function (DUF2063) is likely to bind DNA and that the protein may be involved in transcriptional regulation

Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

Structures of the first representatives of PF06684 (DUF1185) reveal a Bacillus chorismate mutase-like fold with a potential role in amino-acid synthesis

RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution

RNA dependent RNA polymerase (RdRp) is one of the most versatile enzymes of RNA viruses that is indispensable for replicating the genome as well as for carrying out transcription. The core structural features of RdRps are conserved, despite the divergence in their sequences. The structure of RdRp resembles that of a cupped right hand and consists of fingers, palm and thumb subdomains. The catalysis involves the participation of conserved aspartates and divalent metal ions. Complexes of RdRps with substrates, inhibitors and metal ions provide a comprehensive view of their functional mechanism and offer valuable insights regarding the development of antivirals. In this article, we provide an overview of the structural aspects of RdRps and their complexes from the Group III, IV and V viruses and their structure-based phylogeny

Summary of candidate selection and expanded criteria for liver transplantation for hepatocellular carcinoma : a review and consensus statement

The evidence base is poor overall because of the limitedsample sizes of most studies and the heterogeneouscohorts and variables, and few have well-plannedand statistically valid study designs. No studies haveaccounted for the effects of underlying liver diseaseseither before or after LT on overall outcomes, and onlya few studies have assessed the effects of adjuvanttreatments before transplantation. In the majority ofthe reports, the follow-up time is not sufficient forassessing 5-year survival rates. Many have used histologicalfindings from explanted livers to stagepatients, but this has little utility for preoperativestaging and selection for LT. The presence of vascularinvasion, the tumor number and size (also calculatedas the TTV), and the AFP level have most consistentlybeen associated with increased recurrence rates anddiminished survival after LT. Most studies havereported acceptable survival rates for patients meetingthe UCSF criteria; however, it is notable that there aredocumented survival rates for patients with HCCtumors beyond the UCSF criteria that would bemore than acceptable in any other surgicaloncology setting. It is the potential to affect candidateswithout HCC who are also competing for thelimited pool of donor organs that limits the criteria forselecting patients with HCC for LT, especially whenwe consider LT for patients with more advancedstages of HCC

An in silico approach to study the role of epitope order in the multi-epitope-based peptide (MEBP) vaccine design

Abstract With different countries facing multiple waves, with some SARS-CoV-2 variants more deadly and virulent, the COVID-19 pandemic is becoming more dangerous by the day and the world is facing an even more dreadful extended pandemic with exponential positive cases and increasing death rates. There is an urgent need for more efficient and faster methods of vaccine development against SARS-CoV-2. Compared to experimental protocols, the opportunities to innovate are very high in immunoinformatics/in silico approaches, especially with the recent adoption of structural bioinformatics in peptide vaccine design. In recent times, multi-epitope-based peptide vaccine candidates (MEBPVCs) have shown extraordinarily high humoral and cellular responses to immunization. Most of the publications claim that respective reported MEBPVC(s) assembled using a set of in silico predicted epitopes, to be the computationally validated potent vaccine candidate(s) ready for experimental validation. However, in this article, for a given set of predicted epitopes, it is shown that the published MEBPVC is one among the many possible variants and there is high likelihood of finding more potent MEBPVCs than the published candidates. To test the same, a methodology is developed where novel MEBP variants are derived by changing the epitope order of the published MEBPVC. Further, to overcome the limitations of current qualitative methods of assessment of MEBPVC, to enable quantitative comparison and ranking for the discovery of more potent MEBPVCs, novel predictors, Percent Epitope Accessibility (PEA), Receptor specific MEBP vaccine potency (RMVP), MEBP vaccine potency (MVP) are introduced. The MEBP variants indeed showed varied MVP scores indicating varied immunogenicity. Further, the MEBP variants with IDs, SPVC_446 and SPVC_537, had the highest MVP scores indicating these variants to be more potent MEBPVCs than the published MEBPVC and hence should be preferred candidates for immediate experimental testing and validation. The method enables quicker selection and high throughput experimental validation of vaccine candidates. This study also opens the opportunity to develop new software tools for designing more potent MEBPVCs in less time

Biosynthesis of silver nanoparticles from Schizophyllum radiatum HE 863742.1: their characterization and antimicrobial activity

Development of reliable and eco-friendly process for synthesis of silver nanoparticles is an important step in the field of application in nanotechnology. One of the options to achieve this objective is to use natural biological processes. They have an advantage over conventional methods involving chemical agents associated with environmental toxicity. This study demonstrates the extra-cellular synthesis of stable silver nanoparticles using the white rot fungus, Schizophyllum radiatum with GenBank Accession no HE 863742.1. The supernatant of the seed media obtained after separating the cells has been used for the synthesis of silver nanoparticles. The morphology and structure of synthesized silver nanoparticles were characterized using FT-IR, XRD, UV–visible spectrum of the aqueous medium containing silver ion showed a peak in the range of 420–430 nm corresponding to the Plasmon absorbance of silver nanoparticles. Scanning electron microscopy micrograph showed formation of well-dispersed silver nanoparticles in the range of 10–40 nm. The effect of different carbon sources and the time taken for formation particles and the anti-microbial activity of synthesized nanoparticles were carried and compared with silver nitrate solution and with standard streptomycin. The process of reduction being extra-cellular and fast may lead to the development of an easy bioprocess for synthesis of silver nanoparticles