Structure, dynamics, and interactions of jacalin. Insights from molecular dynamics simulations examined in conjunction with results of X‐ray studies

Abstract

Molecular dynamics simulations have been carried out on all the jacalin-carbohydrate complexes of known structure, models of unliganded molecules derived from the complexes and also models of relevant complexes where X-ray structures are not available. Results of the simulations and the available crystal structures involving jacalin permit delineation of the relatively rigid and flexible regions of the molecule and the dynamical variability of the hydrogen bonds involved in stabilizing the structure. Local flexibility appears to be related to solvent accessibility. Hydrogen bonds involving side chains and water bridges involving buried water molecules appear to be important in the stabilization of loop structures. The lectin-carbohydrate interactions observed in crystal structures, the average parameters pertaining to them derived from simulations, energetic contribution of the stacking residue estimated from quantum mechanical calculations, and the scatter of the locations of carbohydrate and carbohydrate-binding residues are consistent with the known thermodynamic parameters of jacalin-carbohydrate interactions. The simulations, along with X-ray results, provide a fuller picture of carbohydrate binding by jacalin than provided by crystallographic analysis alone. The simulations confirm that in the unliganded structures water molecules tend to occupy the positions occupied by carbohydrate oxygens in the lectin-carbohydrate complexes. Population distributions in simulations of the free lectin, the ligands, and the complexes indicate a combination of conformational selection and induced fit.

Role of glycosylation in structure and stability of Erythrina corallodendron lectin (EcorL): A molecular dynamics study

“…Recently, we were able to successfully simulate the effects of demetalation on saccharide binding and the conformational changes in the ion‐binding loop in Concanavalin A 33. Similar studies involving molecular dynamics (MD) simulations on ConA, jacalin, galectin, and other plant lectins have also provided novel insights into their structure and substrate specificity 34–38. This encouraged us to explore in the current study, the effects of glycosylation on the structure and stability of EcorL by comparing the glycosylated and nonglycosylated forms of EcorL using MD simulations.…”

Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of σ-factor activity by proteolysis

“…Clustering of the conformers was based on the α-carbon r.m.s.d. of simulated conformers at different time-points with respect to the crystal structure (39). The normalized population distribution obtained for the RsdA model in the free form (simulations on the RsdA model alone) and the bound form (simulations on the σ D 4 /RsdA complex) resulted in two major peaks in the bound form and three distinct conformational ensembles in the free form (Figure 2a).…”

Effect of linkage on the location of reducing and nonreducing sugars bound to jacalin

“…They have nearly the same tertiary structures, but exhibit different modes of quaternary association . Protein‐sugar interactions at the primary binding site are nearly the same in all the galactose specific β‐prism I fold lectins . The same is true about the interactions at the primary site of the mannose specific β‐prism I fold lectins .…”