Antigens: CarbohydratesII

Abstract

Glycosylation is critical for a wide range of biological processes across both normal and disease states. Carbohydrate antigens, for example, are polymeric chains of diverse monomeric sugar molecules that play a fundamental role in the pathogenicity and virulence of many organisms. Moreover, these pathogen‐associated glycan structures can also be found in association with other types of cells, including tumours. These types of glycan commonalities have helped generate critical discoveries in terms of glycan structure, allowing for the development of working hypotheses for their functions, in addition to the development of agents that target or mediate their expression levels. Therefore, through discussion of glycans as antigens, new insights of key molecular and cellular interactions between them and immune cells can be discerned, and the implication of these interactions in health and disease is enhanced. Numerous reviews and even this ELS series have described the structure of carbohydrates and glycans in general. Key Concepts Glycosylation is the most abundant post‐translational modification of proteins. Glycans expand the chemical diversity of the genetic code. Antigens are a collection of epitopes that affects recognition by the immune system. Antigens and immunogens are very different. Molecular mimicry of glycans profoundly affects the pathophysiology of infection and neoplasia. Lectin‐family receptors and antibodies have been used to define carbohydrate antigens. Clustering of epitopes defines glycan antigens better than nonclustered epitopes. Carbohydrate antigens can define danger signals to the immune system through pattern recognition receptors. Clustering associates with different B‐cell populations for processing as immunogens. MHC and T‐cell receptors see atoms in particular arrays, not as a single molecular species – hence cross‐reactivity with zwitterionic carbohydrate structures. While carbohydrate‐based vaccines have been developed, as cancer vaccines they are not as effective. Metabolism is the next frontier to understanding glycan expression patterns.

Geometric and Electronic Structure Contributions to O–O Cleavage and the Resultant Intermediate Generated in Heme-Copper Oxidases

“…This electronic structure is consistent with the Cu II and Tyr • being EPR-silent, yet it differs from models in the literature that have assumed these S=½ species are antiferromagnetically coupled. 20,50,54,63 While the combination of our DFT calculations and past experimental data offer insight into the mechanism of O-O cleavage in HCOs, as well as the geometric and electronic structure of P m , our conclusions are limited by the experimental data available. Our understanding of the mechanism must draw heavily on the findings for a synthetic model that differs mechanistically from HCOs in both proton transfer and electron transfer.…”

“…52 This has often been assumed to result from antiferromagnetic (AF) coupling between the cu II and the Tyr • . [53][54][55][56] However, this could also result from rapid relaxation associated with the close proximity of three paramagnetic centers (Fe IV , cu II , Tyr = 2.92 Å). The Fe and cu centers are predicted to be AF coupled (J = −5.0 cm −1 ), while the cu-Tyr • pair is predicted to be ferromagnetically coupled (J = +4.4 cm −1 ).…”

NRVS Studies of the Peroxide Shunt Intermediate in a Rieske Dioxygenase and Its Relation to the Native FeII O2 Reaction

“…NRVS spectra were simulated from these heavy mass frequency calculations using the gennrvs script . Molecular orbital contours were generating using LUMO, and Mulliken orbital populations were calculated using QMForge …”

Exceptionally High O–H Bond Dissociation Free Energy of a Dicopper(II) μ-Hydroxo Complex and Insights into the Geometric and Electronic Structure Origins Thereof

“…Density functional theory (DFT) calculations were performed with the electronic structure package Gaussian16 (Revision C01) . Mulliken populations were calculated from the output with QMforge (Version 2.4), and orbitals were visualized in Lumo (Version 1.4b) . The starting structures were adapted from crystallographic coordinates of {[Cu II (TMPA)] 2 (μ-OH)} 3+ and [Cu II (TMPA)­(OH 2 )] 2+ .…”