Nucleoside-Driven Specificity of DNA Methyltransferase.

We have studied the adenosine binding specificities of two bacterial DNA methyltransferases, Taq methyltransferase (M.TaqI), and HhaI methyltransferase (M.HhaI).

Correction to "Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases".

[This corrects the article DOI: 10.1021/jacsau.1c00464.

Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases.

Protein conformational changes can facilitate the binding of noncognate substrates and underlying promiscuous activities. However, the contribution of substrate conformational dynamics to this process is comparatively poorly understood. Here, we analyze human (hMAT2A) and (eMAT) methionine adenosyltransferases that have identical active sites but different substrate specificity.

Implications of divergence of methionine adenosyltransferase in archaea.

Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S-adenosyl methionine from l-methionine and ATP. MAT enzymes are ancient, believed to share a common ancestor, and are highly conserved in all three domains of life. However, the sequences of archaeal MATs show considerable divergence compared with their bacterial and eukaryotic counterparts.

Rossmann-Fold Methyltransferases: Taking a "β-Turn" around Their Cofactor, S-Adenosylmethionine.

Methyltransferases (MTases) are superfamilies of enzymes that catalyze the transfer of a methyl group from S-adenosylmethionine (SAM), a nucleoside-based cofactor, to a wide variety of substrates such as DNA, RNA, proteins, small molecules, and lipids. Depending upon their structural features, the MTases can be further classified into different classes; we consider exclusively the largest class of MTases, the Rossmann-fold MTases. It has been shown that the nucleoside cofactor-binding Rossmann enzymes, particularly the nicotinamide adenine dinucleotide (NAD)-, flavin adenine dinucleotide (FAD)-, and SAM-binding MTases enzymes, share common binding motifs that include a Gly-rich loop region that interacts with the cofactor and a highly conserved acidic residue (Asp/Glu) that interacts with the ribose moiety of the cofactor.

Microarray Analysis of Oligosaccharide-Mediated Multivalent Carbohydrate-Protein Interactions and Their Heterogeneity.

Carbohydrate-protein interactions (CPIs) are involved in a wide range of biological phenomena. Hence, the characterization and presentation of carbohydrate epitopes that closely mimic the natural environment is one of the long-term goals of glycosciences. Inspired by the multivalency, heterogeneity and nature of carbohydrate ligand-mediated interactions, we constructed a combinatorial library of mannose and galactose homo- and hetero-glycodendrons to study CPIs.

Modeling Glyco-Collagen Conjugates Using a Host-Guest Strategy To Alter Phenotypic Cell Migration and in Vivo Wound Healing.

The constructs and study of combinatorial libraries of structurally defined homologous extracellular matrix (ECM) glycopeptides can significantly accelerate the identification of cell surface markers involved in a variety of physiological and pathological processes. Herein, we present a simple and reliable host-guest approach to design a high-throughput glyco-collagen library to modulate the primary and secondary cell line migration process. 4-Amidoadamantyl-substituted collagen peptides and β-cyclodextrin appended with mono- or disaccharides were used to construct self-assembled glyco-collagen conjugates (GCCs), which were found to be thermally stable, with triple-helix structures and nanoneedles-like morphologies that altered cell migration processes.

Exploring the Influence of Shapes and Heterogeneity of Glyco-Gold Nanoparticles on Bacterial Binding for Preventing Infections.

To investigate the effects of the heterogeneity and shape of glyco-nanoprobes on carbohydrate-protein interactions (CPIs), α-d-mannose- and β-d-galactose-linked homo- and heterogeneous glycodendrons were synthesized and immobilized on spherical and rod-shaped gold nanoparticles (AuNPs). Lectin and bacterial binding studies of these glyco-AuNPs clearly illustrate that multivalency and shape of AuNPs contribute significantly to CPIs than the heterogeneity of glycodendrons. Finally, bacterial infection of HeLa cells was effectively inhibited by the homogeneous glycodendron-conjugated rod-shaped AuNPs relative to their heterogeneous counterparts.

Understanding carbohydrate-protein interactions using homologous supramolecular chiral Ru(ii)-glyconanoclusters.

Multivalent glycodendrimers make promising tools to tackle the basic and translational research in the field of carbohydrate-mediated interactions. Despite advances in glycodendrimers and glycopolymers, the multivalent probes available to date are still far from being ideal biological mimics. This work demonstrates the inherent chirality of glycodendrimers to be one of the promising factors to generate different spatial carbohydrate micro-environments to modulate specific carbohydrate-protein interactions.

Correction: Supramolecular metalloglycodendrimers selectively modulate lectin binding and delivery of Ru(ii) complexes into mammalian cells.

Correction for 'Supramolecular metalloglycodendrimers selectively modulate lectin binding and delivery of Ru(ii) complexes into mammalian cells' by Harikrishna Bavireddi, et al., Org. Biomol.

Supramolecular metalloglycodendrimers selectively modulate lectin binding and delivery of Ru(ii) complexes into mammalian cells.

A host-guest interaction between Ru(ii)-complexes and sugar-capped β-cyclodextrin was employed to synthesize metalloglycodendrimers. These glycodendrimers demonstrated selective carbohydrate-protein interactions and controlled the delivery of the Ru(ii) complexes into cancer cells, which may facilitate cell-specific apoptosis. Lectin binding assay revealed micromolar range IC values with different plant lectins.

Effect of Transition Metals on Polysialic Acid Structure and Functions.

Polysialic acid (PSA) is one of the most abundant glycopolymer present in embryonic brain, and it is known to be involved in key roles such as plasticity in the central nervous system, cell adhesion, migration and localization of neurotrophins. However, in adult brain, its expression is quite low. The exception to this is in Alzheimer's disease (AD) brain, where significantly increased levels of polysilylated neural cell adhesion molecule (PSA-NCAM) have been reported.

Immobilization of multivalent glycoprobes on gold surfaces for sensing proteins and macrophages.

The multivalent display of carbohydrates on the cell surface provides cooperative binding to improve the specific biological events. In addition to multivalency, the spatial arrangement and orientation of sugars with respect to external stimuli also trigger carbohydrate-protein interactions. Herein, we report a non-covalent host-guest strategy to immobilize heptavalent glyco-β-cyclodextrin on gold-coated glass slides to study multivalent carbohydrate-protein interactions.

Exploiting the lactose-GM3 interaction for drug delivery.

Protein-protein and protein-carbohydrate interactions as a means to target the cell surface for therapeutic applications have been extensively investigated. However, carbohydrate-carbohydrate interactions (CCIs) have largely been overlooked. Here, we investigate the concept of CCI-mediated drug delivery.

Supramolecular scaffolds on glass slides as sugar based rewritable sensors for bacteria.

We describe here the sugar functionalized β-cyclodextrin-ferrocene glass slides as fully reversible bacterial biosensors under the influence of external adamantane carboxylic acid. The prototype d-mannose - E. coli ORN 178 and l-fucose - P.