Deciphering the structural and biochemical aspects of xylosidase from Pseudopedobacter saltans.

Xylose, a key constituent of the heterogeneous hemicellulose polymer, occurs in lignocellulosic biomass and forms xylan polymers through β-1,4 glycosidic linkages. The β-1,4-xylosidase enzyme was isolated from Pseudopedobacter saltans (PsGH43) to find an effective enzyme with enhanced activity to depolymerize xylo-oligosaccharides. β-1,4-xylosidase belongs to the GH43 family as classified in the Carbohydrate-Active Enzyme Database (CAZy).

Phenotypical mapping of TP53 unique missense mutations spectrum in human cancers.

The p53 tumor suppressor is one of the most mutated genes responsible for tumorigenesis in most human cancers. Out of 29,891 genomic mutations reported in the TP53 Database (https://tp53.isb-cgc.

Clinical Features Predicting COVID-19 Severity Risk at the Time of Hospitalization.

The global spread of COVID-19 has led to significant mortality and morbidity worldwide. Early identification of COVID-19 patients who are at high risk of developing severe disease can help in improved patient management, care, and treatment, as well as in the effective allocation of hospital resources. The severity prediction at the time of hospitalization can be extremely helpful in deciding the treatment of COVID-19 patients.

ECEL1 related distal arthrogryposis 5D in an Indian cohort-Report of recognizable musculoskeletal phenotype and a possible founder variant.

Distal arthrogryposis type 5D (DA5D) is clinically characterized by knee extension contractures, distal joint contractures, clubfoot, micrognathia, ptosis, and scoliosis. We report nine affected individuals from eight unrelated Indian families with DA5D. Although the overall musculoskeletal phenotype is not very distinct from other distal arthrogryposis, the presence of fixed knee extension contractures with or without scoliosis could be an important early pointer to DA5D.

A comprehensive review on role of Aurora kinase inhibitors (AKIs) in cancer therapeutics.

Aurora kinases (AURKs) are a family of serine /threonine protein kinases that have a crucial role in cell cycle process mainly in the event of chromosomal segregation, centrosome maturation and cytokinesis. The family consists of three members including Aurora kinase A (AURK-A), Aurora kinase B (AURK-B) and Aurora kinase C (AURK-C). All AURKs contain a conserved kinase domain for their activity but differ in their cellular localization and functions.

The acidic C-terminal tail of DNA Gyrase of Salmonella enterica serovar Typhi controls DNA relaxation in an acidic environment.

The intracellular bacteria, Salmonella Typhi adapts to acidic conditions in the host cell by resetting the chromosomal DNA topology majorly controlled by DNA Gyrase, a Type II topoisomerase. DNA Gyrase forms a heterodimer AB complex, which manages the DNA supercoiling and relaxation in the cell. DNA relaxation forms a part of the regulatory mechanism to activate the transcription of genes required to survive under hostile conditions.

Structure-based identification of potential natural compound inhibitors targeting bacterial cytoskeleton protein FtsZ from by computational studies.

is one of the multi-drug-resistant pathogens responsible for hospital-acquired infections reported worldwide. Clinically it is challenging to treat these pathogens as they have developed resistance against the existing class of antibiotics. Hence, there is an urgent need to develop a new class of antibiotics against these pathogens to prevent the spread of infections and mortality.

Ceftriaxone-resistant Salmonella Typhi isolated from paediatric patients in north India: Insights into genetic profiles and antibiotic resistance mechanisms.

Purpose: To investigate the antibiotic resistance and genetic profile of ceftriaxone-resistant Salmonella Typhi isolated from the blood culture of two paediatric cases of typhoid fever and one from the stool culture of their household contact, in North India.

Methods: In this study, whole-genome sequencing was carried out with paired-end 2 ​× ​150 bp reads on Illumina MiSeq (Illumina, USA) employing v2 and v3 chemistry. To check data quality, adapters and low-quality sequences were removed through Trimmomatic-v0.

Computational and Biophysical Approaches to Identify Cell Wall-Associated Modulators in Salmonella enterica serovar Typhi.

An increase in the number of antibiotic-resistant bacterial pathogens, in recent times, has posed a great challenge for treating the affected patients. This has paved the way for the development and design of antibiotics against the previously less explored newer targets. Among these, peptidoglycan (PG) biosynthesis serves as a promising target for the design and development of novel drugs.

Flavonoids as potential reactivators of structural mutation p53Y220C by computational and cell-based studies.

The p53 Y220C is one of the most frequently observed structural mutants in various human cancers. The substitution of residue Tyr to Cys makes the p53 DNA binding domain susceptible to solvent entry into the hydrophobic core of the domain thereby destabilizing p53, which results in loss of its tumor suppressor activity. The mutation creates a structural crevice at the region between S3/S4 and S7/S8 loops in the DNA binding domain which can be targeted by small molecules.

Investigating MARK4 inhibitory potential of Bacopaside II: Targeting Alzheimer's disease.

Microtubule affinity regulating kinase 4 (MARK4) is known to hyperphosphorylate tau protein, which subsequently causes Alzheimer's disease (AD). MARK4 is a well-validated drug target for AD; thus, we employed its structural features to discover potential inhibitors. On the other hand, complementary and alternative medicines (CAMs) have been used for the treatment of numerous diseases with little side effects.

Identification of potential biomarkers to predict organ morbidity in COVID-19: A repository based proteomics perspective.

SARS-CoV-2 causes substantial extrapulmonary manifestations in addition to pulmonary disease. Some of the major organs affected are cardiovascular, hematological and thrombotic, renal, neurological, and digestive systems. These types of muti-organ dysfunctions make it difficult and challenging for clinicians to manage and treat COVID-19 patients.

Association of Hsp90 with p53 and Fizzy related homolog (Fzr) synchronizing Anaphase Promoting Complex (APC/C): An unexplored ally towards oncogenic pathway.

The intricate molecular interactions leading to the oncogenic pathway are the consequence of cell cycle modification controlled by a bunch of cell cycle regulatory proteins. The tumor suppressor and cell cycle regulatory proteins work in coordination to maintain a healthy cellular environment. The integrity of this cellular protein pool is perpetuated by heat shock proteins/chaperones, which assist in proper protein folding during normal and cellular stress conditions.

Computational biology: Role and scope in taming antimicrobial resistance.

Background: Infectious diseases pose many challenges due to increasing threat of antimicrobial resistance, which necessitates continuous research to develop novel strategies for development of new molecules with antibacterial activity. In the era of computational biology there are tools and techniques available to address and solve the disease management issues in the field of clinical microbiology. The sequencing techniques, structural biology and machine learning can be implemented collectively to tackle infectious diseases e.

Effect of Double Mutation (L452R and E484Q) on the Binding Affinity of Monoclonal Antibodies (mAbs) against the RBD-A Target for Vaccine Development.

The COVID-19 pandemic, caused by SARS-CoV-2, emerges as a global health problem, as the viral genome is evolving rapidly to form several variants. Advancement and progress in the development of effective vaccines and neutralizing monoclonal antibodies are promising to combat viral infections. In the current scenario, several lineages containing "co-mutations" in the receptor-binding domain (RBD) region of the spike (S) protein are imposing new challenges.

Structure of the complex of camel peptidoglycan recognition protein-S with hexanoic acid reveals novel features of the versatile ligand-binding site at the dimeric interface.

The short peptidoglycan recognition protein (PGRP-S) of the innate immune system recognizes the invading microbes through binding to their cell wall molecules. In order to understand the mode of binding of PGRP-S to bacterial cell wall molecules, the structure of the complex of camel PGRP-S (CPGRP-S) with hexanoic acid has been determined at 2.07 Å resolution.

Computational and Biophysical Characterization of Heterocyclic Derivatives of Anthraquinone against Human Aurora Kinase A.

Human Aurora kinase A (AurA) has recently garnered the attention of researchers worldwide as a promising effective mitotic drug target for its involvement in cancer and related inflammatory anomalies. This study has explored the binding affinity of newly identified heteroarene-fused anthraquinone derivatives against AurA. Molecular docking analyses showed that all the heteroanthraquinone compounds bind to AurA with different affinities.

Genomic and structural mechanistic insight to reveal the differential infectivity of omicron and other variants of concern.

Background: The genome of SARS-CoV-2, is mutating rapidly and continuously challenging the management and preventive measures adopted and recommended by healthcare agencies. The spike protein is the main antigenic site that binds to the host receptor hACE-2 and is recognised by antibodies. Hence, the mutations in this site were analysed to assess their role in differential infectivity of lineages having these mutations, rendering the characterisation of these lineages as variants of concern (VOC) and variants of interest (VOI).

Identification of natural small molecule modulators of MurB from Salmonella enterica serovar Typhi Ty2 strain using computational and biophysical approaches.

The increase of antibiotic-resistant bacterial pathogens has created challenges in treatment and warranted the design of antibiotics against comparatively less exploited targets. The peptidoglycan (PG) biosynthesis delineates unique pathways for the design and development of a novel class of drugs. Mur ligases are an essential component of bacterial cell wall synthesis that play a pivotal role in PG biosynthesis to maintain internal osmotic pressure and cell shape.

Ligand recognition by peptidoglycan recognition protein-S (PGRP-S): structure of the complex of camel PGRP-S with heptanoic acid at 2.15 Å resolution.

Peptidoglycan recognition proteins (PGRPs) are important components of the innate immune system which provide the first line of defense against invading microbes. There are four members in the family of PGRPs in animals of which PGRP-S is a common domain. It is responsible for the binding to microbial cell wall molecules.

Structural insights of a putative β-1,4-xylosidase (PsGH43F) of glycoside hydrolase family 43 from Pseudopedobacter saltans.

Structural and conformational insights of a putative β-1,4-xylosidase (PsGH43F) of glycoside hydrolase family 43 from Pseudopedobacter saltans were investigated by computational and Circular Dichroism (CD) analyses. PsGH43F was cloned and expressed in E. coli BL21 (DE3) cells and the purified enzyme gave the size ~50 kDa on SDS-PAGE analysis.

Targeting novel sites in DNA gyrase for development of anti-microbials.

Antimicrobial resistance in bacteria poses major challenges in selection of the therapeutic regime for managing the infectious disease. There is currently an upsurge in the appearance of multiple drug resistance in bacterial pathogens and a decline in the discovery of novel antibiotics. DNA gyrase is an attractive target used for antibiotic discovery due to its vital role in bacterial DNA replication and segregation in addition to its absence in mammalian organisms.

Mechanism of apoptosis activation by Curcumin rescued mutant p53Y220C in human pancreatic cancer.

The mutant p53Y220C (mutp53Y220C) is frequently observed in numerous tumors, including pancreatic cancer. The mutation creates a crevice in the DNA binding core domain and makes p53 a thermally unstable non-functional protein that assists tumor progression and confers resistance to chemotherapeutic drugs. Restoring mutp53 function to its wild type by selectively targeting this crevice with small molecules is a pivotal strategy to promote apoptosis.

Identification of a promising inhibitor from (star anise) against the main protease of SARS-CoV-2: insights from the computational study.

SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (M) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus.