Engineered Carbohydrate-Recognition Domains for Glycoproteomic Analysis of Cell Surface Glycosylation and Ligands for Glycan-Binding Receptors

Powlesland, Alex S.; Quintero-Martínez, Adrián; Lim, Paik Gee; Pipirou, Zoi; Taylor, Maureen E.; Drickamer, Kurt

doi:10.1016/s0076-6879(10)80009-6

Cited by 9 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it seems reasonable that glucose, which has the same configuration regarding 3-and 4-hydroxy groups as mannose, can bind to EPNH-CEL-I with a moderate affinity. Along with the findings of the preceding studies on engineering of MBP-A to change its specificity to galactose binding [14,15] and its applications for the identification of cell surface glycoconjugates [38][39][40], a reversal change in the specificity of CEL-I from galactose (N-acetylgalactosamine) to mannose shown in the present study suggests the versatility of C-type CRDs. As observed in glycoconjugate microarray analysis, mutations in CEL-I seem to have affected the recognition of not only monosaccharides but also oligosaccharides.…”

Section: Effects Of the Residues At Position 105 On Binding Specificitysupporting

confidence: 82%

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis

Moriuchi

Unno

Goda

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Section: Effects Of the Residues At Position 105 On Binding Specificitysupporting

confidence: 82%

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis

Moriuchi

Unno

Goda

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

“…One of the most important biological processes at the molecular level is the formation of protein–ligand complexes. Proteins need to recognize, bind and discriminate properly among a universe of possible ligands in order to perform their function, and thus determining the structure and underlying key interactions of particular protein–ligand complexes is of paramount relevance. , This knowledge is also very important for the rational design of new and more effective drugs, − therefore several experimental and in silico tools have been developed in the last decades to determine and analyze them. , Together with X-ray crystallography (and NMR to a lesser extent) of protein–ligand complexes, small molecular fragments and/or water miscible solvents can be used to identify specific types (e.g., hydrophilic, hydrophobic, charged) of potential protein–ligand interaction sites. − For example, solvent mapping, as used in the multiple solvent crystal structures (MSCS) technique, , consists in solving crystal structures of proteins in the presence of several organic cosolvents, enforcing the idea that small molecules binding to specific sites on the protein reveal key interaction sites. Therefore, optimal ligands should be built displaying a chemical structure that is able to perform these same interactions.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics in Mixed Solvents Reveals Protein–Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions

Arcon

Defelipe

Modenutti

et al. 2017

J. Chem. Inf. Model.

View full text Add to dashboard Cite

One of the most important biological processes at the molecular level is the formation of protein-ligand complexes. Therefore, determining their structure and underlying key interactions is of paramount relevance and has direct applications in drug development. Because of its low cost relative to its experimental sibling, molecular dynamics (MD) simulations in the presence of different solvent probes mimicking specific types of interactions have been increasingly used to analyze protein binding sites and reveal protein-ligand interaction hot spots. However, a systematic comparison of different probes and their real predictive power from a quantitative and thermodynamic point of view is still missing. In the present work, we have performed MD simulations of 18 different proteins in pure water as well as water mixtures of ethanol, acetamide, acetonitrile and methylammonium acetate, leading to a total of 5.4 μs simulation time. For each system, we determined the corresponding solvent sites, defined as space regions adjacent to the protein surface where the probability of finding a probe atom is higher than that in the bulk solvent. Finally, we compared the identified solvent sites with 121 different protein-ligand complexes and used them to perform molecular docking and ligand binding free energy estimates. Our results show that combining solely water and ethanol sites allows sampling over 70% of all possible protein-ligand interactions, especially those that coincide with ligand-based pharmacophoric points. Most important, we also show how the solvent sites can be used to significantly improve ligand docking in terms of both accuracy and precision, and that accurate predictions of ligand binding free energies, along with relative ranking of ligand affinity, can be performed.

show abstract

“…30 The knowledge of the key forces involved in sugar recognition has been also employed for protein engineering. For instance, specifically-designed mutagenesis experiments have been elegantly employed for achieving galactose recognition, starting from a mannose-binding protein 34 .…”

Section: Affinity and Selectivitymentioning

confidence: 99%

Carbohydrate–Aromatic Interactions

et al. 2012

View full text Add to dashboard Cite

The recognition of saccharides by proteins has far reaching implications in biology, technology, and drug design. Within the past two decades, researchers have directed considerable effort toward a detailed understanding of these processes. Early crystallographic studies revealed, not surprisingly, that hydrogen-bonding interactions are usually involved in carbohydrate recognition. But less expectedly, researchers observed that despite the highly hydrophilic character of most sugars, aromatic rings of the receptor often play an important role in carbohydrate recognition. With further research, scientists now accept that noncovalent interactions mediated by aromatic rings are pivotal to sugar binding. For example, aromatic residues often stack against the faces of sugar pyranose rings in complexes between proteins and carbohydrates. Such contacts typically involve two or three CH groups of the pyranoses and the π electron density of the aromatic ring (called CH/π bonds), and these interactions can exhibit a variety of geometries, with either parallel or nonparallel arrangements of the aromatic and sugar units. In this Account, we provide an overview of the structural and thermodynamic features of protein-carbohydrate interactions, theoretical and experimental efforts to understand stacking in these complexes, and the implications of this understanding for chemical biology. The interaction energy between different aromatic rings and simple monosaccharides based on quantum mechanical calculations in the gas phase ranges from 3 to 6 kcal/mol range. Experimental values measured in water are somewhat smaller, approximately 1.5 kcal/mol for each interaction between a monosaccharide and an aromatic ring. This difference illustrates the dependence of these intermolecular interactions on their context and shows that this stacking can be modulated by entropic and solvent effects. Despite their relatively modest influence on the stability of carbohydrate/protein complexes, the aromatic platforms play a major role in determining the specificity of the molecular recognition process. The recognition of carbohydrate/aromatic interactions has prompted further analysis of the properties that influence them. Using a variety of experimental and theoretical methods, researchers have worked to quantify carbohydrate/aromatic stacking and identify the features that stabilize these complexes. Researchers have used site-directed mutagenesis, organic synthesis, or both to incorporate modifications in the receptor or ligand and then quantitatively analyzed the structural and thermodynamic features of these interactions. Researchers have also synthesized and characterized artificial receptors and simple model systems, employing a reductionistic chemistry-based strategy. Finally, using quantum mechanics calculations, researchers have examined the magnitude of each property's contribution to the interaction energy.

show abstract

Engineered Carbohydrate-Recognition Domains for Glycoproteomic Analysis of Cell Surface Glycosylation and Ligands for Glycan-Binding Receptors

Cited by 9 publications

References 29 publications

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis

Molecular Dynamics in Mixed Solvents Reveals Protein–Ligand Interactions, Improves Docking, and Allows Accurate Binding Free Energy Predictions

Carbohydrate–Aromatic Interactions

Contact Info

Product

Resources

About