Lectin engineering: the possible and the actual

Abstract

Lectins are a widespread group of sugar-binding proteins occurring in all types of organisms including animals, plants, bacteria, fungi and even viruses. According to a recent report, there are more than 50 lectin scaffolds (∼Pfam), for which three-dimensional structures are known and sugar-binding functions have been confirmed in the literature, which far exceeds our view in the twentieth century (Fujimoto et al. 2014 Methods Mol. Biol. 1200 , 579–606 ( doi:10.1007/978-1-4939-1292-6_46 )). This fact suggests that new lectins will be discovered either by a conventional screening approach or just by chance. It is also expected that new lectin domains including those found in enzymes as carbohydrate-binding modules will be generated in the future through evolution, although this has never been attempted on an experimental level. Based on the current state of the art, various methods of lectin engineering are available, by which lectin specificity and/or stability of a known lectin scaffold can be improved. However, the above observation implies that any protein scaffold, including those that have never been described as lectins, may be modified to acquire a sugar-binding function. In this review, possible approaches to confer sugar-binding properties on synthetic proteins and peptides are described.

The challenges of glycan recognition with natural and artificial receptors

“…In order to improve their binding properties, researchers have started to focus their efforts on lectin engineering. [92][93][94][95][96][97] Several types of lectins can be used as scaffolds, such as L-type, F-type, Galectins and R-type, with different engineering procedures available (e.g. site-directed mutagenesis, random mutagenesis and DNA shuffle to name a few).…”

Functional reprogramming of Candida glabrata epithelial adhesins: the role of conserved and variable structural motifs in ligand binding

“…In general, our study underscores the view that deciphering the sugar code and successful lectin engineering are challenging tasks that crucially depend on highly detailed structural and functional studies on glycan-lectin interactions (30,31). Our study clearly shows that reaching these goals not only depends on uncovering novel lectin folds, but in addition requires extensive functional analysis.…”

A Two-Dimensional Affinity Capture and Separation Mini-Platform for the Isolation, Enrichment, and Quantification of Biomarkers and Its Potential Use for Liquid Biopsy

“…They are used as an effective tool for the targeting, separation, and reliable identification of glycoprotein molecules. Their importance stems from the understanding that changes in glycoprotein and glycopeptide content, altered glycosylations, and aberrant glycan structures are increasingly recognized as cancer hallmarks [ 162 , 163 , 164 , 165 ].…”