Molecular modeling, docking and dynamics simulations of the Dioclea lasiophylla Mart. Ex Benth seed lectin: An edematogenic and hypernociceptive protein

Abstract

Lectins are proteins, or glycoproteins, capable of reversibly binding to specific mono- or oligosaccharides via a noncatalytic domain. The Diocleinae subtribe presents lectins with high structural similarity, but different effects based on biological activity assays. This variability results from small structural differences. Therefore, in this context, the present study aimed to perform a structural analysis of the lectin from Dioclea lasiophylla Mart. ex Benth seeds (DlyL) and evaluate its inflammatory effect. To accomplish this, DlyL was purified in a single step by affinity chromatography on Sephadex G-50 matrix. DlyL primary structure was determined through a combination of tandem mass spectrometry and DNA sequencing. DlyL showed high similarity with other species from the same genus. Its theoretical three-dimensional structure was predicted by homology modelling, and the protein was subjected to ligand screening with monosaccharides, oligosaccharides and complex N-glycans by molecular docking. Stability and binding of the lectin with α-methyl-d-mannoside were assessed by molecular dynamics. DlyL showed acute inflammatory response with hypernociceptive effect in the paw edema model, possibly by interaction with glycans present at the cell surface.

ConA-Like Lectins: High Similarity Proteins as Models to Study Structure/Biological Activities Relationships

“…Many inflammatory processes promoted by these lectins are accompanied by hypernociception. For example, when injected subcutaneously intraplantar in rats, DlyL and CvilL induced paw edema and increased the sensitivity of paws, as evaluated by the application of von Frey filaments [20,44]. However, when administered intravenously or orally, they demonstrate antinociceptive effects.…”

“…ConA primary structure was determined in 1975 by Cunningham and colleagues [94] by Edman degradation, and, since then, 22 ConA-like lectins from the Diocleinae subtribe have had their primary structures determined using Edman degradation, as well as mass spectrometry and DNA sequencing: ConV [36] (Uniprot id: C0HJY1), CGL (Uniprot id: P14894), ConM [95] (Uniprot id: P81364), ConBr [96] (Uniprot id: P55915), CboL [97] (Uniprot id: A0A023GPI8), CaBo [98] (Uniprot id: P58906), ConGF [99] (Uniprot id: A0A067XG71), DvirL (Uniprot id: P58907), CRL1 [42] (P86184), DLL [63] (PDB id: 5UUY), DlyL [44] (Uniprot id: C0HK27), DRL [100] (Uniprot id: P58908), DguiL [101] (Uniprot id: P81637), DGL [101] (Uniprot id: P08902), Cramoll [102] (Uniprot id: P83721), CFL [101] (Uniprot id: P81517), DVL (Uniprot id: I1SB09), Camptosema pedicaellatum lectin (CPL) [103] (Uniprot id: J9PBR3), DSL [104] (Uniprot id: B3EWJ2), DWL [38] (Uniprot id: P86624), DrfL [52] (Uniprot id: C0HK81) and Dioclea lehmanni lectin (DlehL) [95].…”

“…Through a water bridge, the calcium ion can interact with the main chain atoms of that cis-peptide, which is at the base of the CRD and is responsible for stabilizing the carbohydrates within the site cavity [113]. The importance of this cis-peptide was demonstrated through structural studies by crystallography and molecular modeling, as well as molecular docking and dynamics involving CaBo, DlyL and DrfL [44,52,114]. Figure 3B,C demonstrates both sites for four Diocleinae lectins.…”

Exploring the carbohydrate‐binding ability of Canavalia bonariensis lectin in inflammation models

“…In the paw edema test, the α-methyl-mannoside reversal assay ( Figure 4C The results presented in this paper are consistent with those shown in other works described for ConA-like lectins, in particular those describing the proinflammatory effect of lectins isolated from the Diocleineae subtribe, as reported also for the lectins from Dioclea lasiophylla and Canavalia virosa. 23,34,35 Thus, it is notorious that, even working with a group of lectins of high structural similarity and of the same specificity, the results of biological activity vary in terms of the potency of the biological effect, which justifies all the more acute tests regarding the fine specificity of these proteins.…”

“…This web tool had not been previously used for this type of screening with ConA-like lectin, although the results presented here are closely related the experimental interactions by molecular docking, already widely explored in these structure-function studies. 6,34,36 The search for varied information regarding the binding of CaBo by mannosidic glycans arouses particular interest due to the fact that these glycans are present in the common core of N-glycosylation.…”