Binding diversity of the two binding sites of ricin B lectin

Ganguly, Debabani; Mukhopadhyay, Chaitali

doi:10.1002/bip.20530

Cited by 17 publications

(14 citation statements)

References 44 publications

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“…At neutral pH, however, the formation of a salt bridge between Arg236 and Glu199 favours the establishment of a H-bond between N E (Arg236) and the 6 0 -hydroxyl group. MD runs revealed the presence of the contacts but they were not stable throughout the simulation, as similarly reported recently [23]. In VAAÕs Tyr-site, Arg236 and Glu199 are replaced by Ala and Ser, respectively, precluding such a pH-dependent switch for VAA, which tolerates a2,6-sialylation well compared to ricin [24,25].…”

Section: Discussionsupporting

confidence: 59%

Domain versatility in plant AB‐toxins: Evidence for a local, pH‐dependent rearrangement in the 2γ lectin site of the mistletoe lectin by applying ligand derivatives and modelling

et al. 2008

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Mistletoe lectin is a potent biohazard. Lectin activity in the toxic dimer primarily originates from the 2c-subdomain (Tyr-site) of the B-subunit. Crystallographic information on lectin-sugar complexes is available only at acidic pH, where lectin activity is low. Thus, we mapped ligand-binding properties including comparison to ricinÕs Tyr-site at neutral pH. Using these results and molecular dynamics simulations, a local conformational change was rendered likely. The obtained structural information is valuable for the design of potent inhibitors.

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Section: Discussionsupporting

confidence: 59%

Domain versatility in plant AB‐toxins: Evidence for a local, pH‐dependent rearrangement in the 2γ lectin site of the mistletoe lectin by applying ligand derivatives and modelling

et al. 2008

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“…The binding of oligosaccharide is quite stronger than that of the mono-or disaccharides as found in our previous study on ricin B chain-carbohydrate interaction. 37 This is in conformity with the experimental findings, which is a natural phenomenon for all lectins. From earlier experimental studies it was known that the association constant of this oligosaccharide 14 binding to ricin is 7 3 10 6 M…”

Section: Discussionsupporting

confidence: 90%

“…The potency of the binding sites has been changed when the ligand terminal was inverted. The weak binding potency of the 2nd binding site as observed from our previous study 37 has changed to stronger potency. Thus, not only the ligand specificity but also the specificity of the particular terminal for the biantennary ligand (ligand environment) is important for sugar binding.…”

Section: Discussionmentioning

confidence: 70%

“…For the 2nd binding site within 5 Å of the oligosaccharide Val235, Ala237, and Ile246 are present. It was observed from our previous study 37 that only Trp37 for binding site 1 and 237Ala for binding site 2 are involved in hydrophobic interaction with the mono-/disaccharide. For oligosaccharide binding increased number of hydrophobic residues present near the binding site promote the overall binding.…”

Section: Structure and Dynamics Of Rtb-oligosaccharide Complexesmentioning

confidence: 90%

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Extended binding site of ricin B lectin for oligosaccharide recognition

Ganguly¹,

Mukhopadhyay²

2007

Biopolymers

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The plant lectin ricin B chain binds oligosaccharide with more affinity than the mono- or disaccharide ligands. The experiments indicated that a biantennary oligosaccharide could bind itself to any of the crystallographically established 1st or 2nd binding sites. After manual docking of either terminal galactose residues of the oligosaccharide in the 1st and 2nd binding sites of Ricin B and simulating the systems over nanosecond trajectories in implicit solvent, it was observed that the protein bound the oligosaccharide strongly through both its 1st and 2nd binding sites. Not only were the terminal galactose residues, several other residues of the oligosaccharide were involved in the binding scheme. Average gas phase energies were calculated molecular mechanically, solvation energies were calculated by Generalized Born model and the normal mode analysis was used to calculate the entropic contribution of binding. The entropy/enthalpy compensation has been observed for the protein-oligosaccharide interactions. The binding was found to be enthalpically favorable and compensating for the unfavorable entropic contribution. Comparison of the calculated free energy with the experimental data clearly suggests that binding is mono-dentate rather than bi-dentate through a single Gal-containing antenna.

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“…23 In the current study, we did not perform the perturbation calculation which spreads the efforts along "reaction" pathway. Rather we focus on all the sampling at the end-point states, the apo and complex states.…”

Section: ' Results and Discussionmentioning

confidence: 99%

Stability and Sugar Recognition Ability of Ricin-like Carbohydrate Binding Domains

et al. 2011

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Lectins are a class of proteins known for their novel binding to saccharides. Understanding this sugar recognition process can be crucial in creating structure-based designs of proteins with various biological roles. We focus on the sugar binding of a particular lectin, ricin, which has two β-trefoil carbohydrate-binding domains (CRDs) found in several plant protein toxins. The binding ability of possible sites of ricin-like CRD has been puzzling. The apo and various (multiple) ligand-bound forms of the sugar-binding domains of ricin were studied by molecular dynamics simulations. By evaluating structural stability, hydrogen bond dynamics, flexibility, and binding energy, we obtained a detailed picture of the sugar recognition of the ricin-like CRD. Unlike what was previously believed, we found that the binding abilities of the two known sites are not independent of each other. The binding ability of one site is positively affected by the other site. While the mean positions of different binding scenarios are not altered significantly, the flexibility of the binding pockets visibly decreases upon multiple ligand binding. This change in flexibility seems to be the origin of the binding cooperativity. All the hydrogen bonds that are strong in the monoligand state are also strong in the double-ligand complex, although the stability is much higher in the latter form due to cooperativity. These strong hydrogen bonds in a monoligand state are deemed to be the essential hydrogen bonds. Furthermore, by examining the structural correlation matrix, the two domains are structurally one entity. Galactose hydroxyl groups, OH4 and OH3, are the most critical parts in both site 1α and site 2γ recognition.

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Binding diversity of the two binding sites of ricin B lectin

Cited by 17 publications

References 44 publications

Domain versatility in plant AB‐toxins: Evidence for a local, pH‐dependent rearrangement in the 2γ lectin site of the mistletoe lectin by applying ligand derivatives and modelling

Domain versatility in plant AB‐toxins: Evidence for a local, pH‐dependent rearrangement in the 2γ lectin site of the mistletoe lectin by applying ligand derivatives and modelling

Extended binding site of ricin B lectin for oligosaccharide recognition

Stability and Sugar Recognition Ability of Ricin-like Carbohydrate Binding Domains

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