De novo drug designing coupled with brute force screening and structure guided lead optimization gives highly specific inhibitor of METTL3: a potential cure for Acute Myeloid Leukaemia.

Expression of METTL3, a SAM dependent methyltransferase, which deposits m6A on mRNA is linked to poor prognosis in Acute Myeloid Leukaemia and other type of cancers. Down regulation of this epitranscriptomic regulator has been found to inhibit cancer progression. Silencing the methyltransferase activity of METTL3 is a lucrative strategy to design anticancer drugs.

Brute Force Virtual Drug Screening with Molecular Dynamics Simulation and MM/PBSA to Find Potent Inhibitors of METTL16.

Epitranscriptomic modification is a dynamic modification of RNAs. Epitranscriptomic writer proteins are methyltransferases, such as METTL3 and METTL16. The up regulation of METTL3 have been found to be linked to different cancers and targeting METTL3 is an effective way to reduce tumour progression.

Amentoflavone and methyl hesperidin, novel lead molecules targeting epitranscriptomic modulator in acute myeloid leukemia: in silico drug screening and molecular dynamics simulation approach.

Introduction: MA modification in transcriptome is critical in regulating different cellular processes, including cancer. In human beings, METTL3 is the major mA writer that works in association with METTL14, an accessory protein. Extensive study revealed that cancer progression for acute myeloid leukemia, gastric cancer, colorectal cancer, hepatocellular carcinoma, and lung cancer is directly contributed by irregular expression of METTL3.

The DEAH-box RNA helicase Dhr1 contains a remarkable carboxyl terminal domain essential for small ribosomal subunit biogenesis.

Ribosome biogenesis is an essential process in all living cells, which entails countless highly sequential and dynamic structural reorganization events. These include formation of dozens RNA helices through Watson-Crick base-pairing within ribosomal RNAs (rRNAs) and between rRNAs and small nucleolar RNAs (snoRNAs), transient association of hundreds of proteinaceous assembly factors to nascent precursor (pre-)ribosomes, and stable assembly of ribosomal proteins. Unsurprisingly, the largest group of ribosome assembly factors are energy-consuming proteins (NTPases) including 25 RNA helicases in budding yeast.

Elucidation of the mechanism of disulfide exchange between staphylococcal thioredoxin2 and thioredoxin reductase2: A structural insight.

The redox homeostasis of cytoplasm is maintained by a series of disulfide exchange reactions mediated by proteins belonging to the thioredoxin superfamily. Thioredoxin and thioredoxin reductase, being the major members of the family, play a key role in oxidative stress response of Staphylococcus aureus. In this report, we have identified and characterised an active thioredoxin system of the mentioned pathogen.

Reconstitution of the RNA-dependent RNA polymerase activity of Antheraea mylitta cypovirus in vitro using separately expressed different functional domains of the enzyme.

Antheraea mylitta cytoplasmic polyhedrosis virus is a segmented dsRNA virus of the family Reoviridae. Segment 2 (S2)-encoded RNA-dependent RNA polymerase (RdRp) helps the virus to propagate its genome in the host cell of the silkworm, Antheraea mylitta. Cloning, expression, purification and functional analysis of individual domains of RdRp have demonstrated that the purified domains interact in vitro.

Complete catalytic cycle of cofactor-independent phosphoglycerate mutase involves a spring-loaded mechanism.

Cofactor-independent phosphoglycerate mutase (iPGM), an important enzyme in glycolysis and gluconeogenesis, catalyses the isomerization of 2- and 3-phosphoglycerates by an Mn(2+)-dependent phospho-transfer mechanism via a phospho-enzyme intermediate. Crystal structures of bi-domain iPGM from Staphylococcus aureus, together with substrate-bound forms, have revealed a new conformation of the enzyme, representing an intermediate state of domain movement. The substrate-binding site and the catalytic site are present in two distinct domains in the intermediate form.

Expression, purification, crystallization and preliminary X-ray diffraction studies of phosphoglycerate mutase from Staphylococcus aureus NCTC8325.

Phosphoglycerate mutase (PGM) is a key enzyme in carbohydrate metabolism. It takes part in both glycolysis and gluconeogenesis. PGM from pathogenic Staphylococcus aureus (NCTC8325) was cloned in pQE30 expression vector overexpressed in Escherichia coli M15 (pREP4) cells and purified to homogeneity.

Crystal structure of hexanoyl-CoA bound to β-ketoacyl reductase FabG4 of Mycobacterium tuberculosis.

FabGs, or β-oxoacyl reductases, are involved in fatty acid synthesis. The reaction entails NADPH/NADH-mediated conversion of β-oxoacyl-ACP (acyl-carrier protein) into β-hydroxyacyl-ACP. HMwFabGs (high-molecular-weight FabG) form a phylogenetically separate group of FabG enzymes.

Crystal structures of triosephosphate isomerase from methicillin resistant Staphylococcus aureus MRSA252 provide structural insights into novel modes of ligand binding and unique conformations of catalytic loop.

Staphylococcus aureus is one of the most dreaded pathogens worldwide and emergence of notorious antibiotic resistant strains have further exacerbated the present scenario. The glycolytic enzyme, triosephosphate isomerase (TIM) is one of the cell envelope proteins of the coccus and is involved in biofilm formation. It also plays an instrumental role in adherence and invasion of the bacteria into the host cell.

Expression, purification, crystallization and preliminary X-ray diffraction studies of phosphoglycerate kinase from methicillin-resistant Staphylococcus aureus MRSA252.

Phosphoglycerate kinase (PGK) from methicillin-resistant Staphylococcus aureus MRSA252 has been cloned in pQE30 expression vector, overexpressed in Escherichia coli SG13009 (pREP4) cells and purified to homogeneity. The protein was crystallized from 0.15 M CaCl(2), 0.